RESUMEN
BACKGROUND: Pneumocystis jirovecii is the most emerging life-threating health problem that causes acute and fatal pneumonia infection. It is rare and more contagious for patients with leukemia and immune-deficiency disorders. Until now there is no treatment available for this infection therefore, it is needed to develop any treatment against this pathogen. METHODS: In this work, we used comparative proteomics, robust immune-informatics, and reverse vaccinology to create an mRNA vaccine against Pneumocystis jirovecii by targeting outer and transmembrane proteins. Using a comparative subtractive proteomic analysis of two Pneumocystis jirovecii proteomes, a distinct non-redundant Pneumocystis jirovecii (strain SE8) proteome was chosen. Seven Pneumocystis jirovecii transmembrane proteins were chosen from this proteome based on hydrophilicity, essentiality, virulence, antigenicity, pathway interaction, protein-protein network analysis, and allergenicity. OBJECTIVE: The reverse vaccinology approach was used to predict the immunogenic and antigenic epitopes of major histocompatibility complex (MHC) I, II and B-cells from the selected proteins on the basis of their antigenicity, toxicity and allergenicity. These immunogenic epitopes were linked together to construct the mRNA-based vaccine. To enhance the immunogenicity, suitable adjuvant, linkers (GPGPG, KK, and CYY), and PRDRE sequences were used. RESULTS: Through predictive modeling and confirmation via the Ramachandran plot, we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct's immunogenicity (GRAVY index: -0.271, instability index: 39.53, antigenicity: 1.0428). The physiochemical profiling of vaccine construct was predicted it an antigenic, efficient, and potential vaccine. Notably, strong interactions were observed between the vaccine construct and TLR-3/TLR-4 (-1301.7 kcal/mol-1 and -1374.7 kcal/mol-1). CONCLUSIONS: The results predicted that mRNA-based vaccines trigger a cellular and humoral immune response, making the vaccine potential candidate against Pneumocystis jirovecii and it is more suitable for in-vitro analysis and validation to prove its effectiveness.
Asunto(s)
Pneumocystis carinii , Neumonía por Pneumocystis , Proteómica , Vacunología , Vacunas de ARNm , Proteómica/métodos , Pneumocystis carinii/inmunología , Pneumocystis carinii/genética , Humanos , Vacunología/métodos , Vacunas de ARNm/inmunología , Neumonía por Pneumocystis/prevención & control , Neumonía por Pneumocystis/inmunología , Neumonía por Pneumocystis/microbiología , Vacunas Fúngicas/inmunología , Proteínas Fúngicas/inmunología , Proteínas Fúngicas/genética , Proteoma/inmunología , ARN Mensajero/genética , ARN Mensajero/inmunología , Desarrollo de Vacunas/métodos , Vacunas Sintéticas/inmunologíaRESUMEN
Seronegative human immunodeficiency virus (HIV) infection, where an HIV-specific antibody response is lacking even in chronic or late-stage HIV infections, is extremely rare. Here, we report the case of a 50-year-old Japanese man presenting with Pneumocystis pneumonia who did not produce antibodies against HIV-1 until the initiation of antiretroviral therapy (ART). Fourth-generation antigen-antibody testing temporarily reverted from weakly positive to negative soon after initiating ART, likely due to a reduction in viral load (assessed by p24 antigen levels). His HIV-1 antibody titers remained low or indeterminate even after four years of ART. A literature review suggested that the absence of HIV-1-specific antibody production may be associated with unimpeded HIV replication and rapid CD4+ T cell decline. Seronegative HIV infection can lead to deferred diagnosis and treatment, thereby increasing the risk of transmitting the virus to others or developing opportunistic illnesses. It is important to combine multiple tests for diagnosis, depending on the medical condition. Further studies are required to investigate the host factors involved in the production of HIV-1-specific antibodies.
Asunto(s)
Infecciones por VIH , VIH-1 , Neumonía por Pneumocystis , Humanos , Masculino , Neumonía por Pneumocystis/diagnóstico , Neumonía por Pneumocystis/inmunología , Neumonía por Pneumocystis/microbiología , Persona de Mediana Edad , VIH-1/inmunología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Anticuerpos Anti-VIH/sangre , Anticuerpos Anti-VIH/inmunología , Carga Viral , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Seronegatividad para VIH , Formación de Anticuerpos , Pneumocystis carinii/aislamiento & purificación , Pneumocystis carinii/inmunología , Pueblos del Este de AsiaRESUMEN
To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/ targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >1530mg of prednisolone or equivalent for >24 weeks. These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.
Asunto(s)
Humanos , Enfermedades Autoinmunes/complicaciones , Infecciones Oportunistas/etiología , Enfermedades Reumáticas/complicaciones , Triaje/normas , Prevención de Enfermedades , Antivirales/uso terapéutico , Tuberculosis/prevención & control , Hepatitis C/prevención & control , Herpesvirus Humano 3 , Pneumocystis carinii/inmunología , Profilaxis Posexposición , Hepatitis B/prevención & controlRESUMEN
Background: Pneumocystis jiroveci pneumonia (PJP) is the most common opportunistic infection in immunocompromised patients. The accurate prediction of PJP development in patients undergoing immunosuppressive therapy remains challenge. Methods: Patients undergoing immunosuppressive treatment and with confirmed pneumocystis jiroveci infection were enrolled. Another group of matched patients with immunosuppressant treatment but without signs of infectious diseases were enrolled to control group. Results: A total of 80 (40 PJP, 40 non-PJP) participants were enrolled from Tongji Hospital. None of the patients were HIV positive. The routine laboratory indicators, such as LYM, MON, RBC, TP, and ALB, were significantly lower in PJP patients than in non-PJP patients. Conversely, LDH in PJP patients was significantly higher than in non-PJP controls. For immunological indicators, the numbers of T, B, and NK cells were all remarkably lower in PJP patients than in non-PJP controls, whereas the functional markers such as HLA-DR, CD45RO and CD28 expressed on CD4+ or CD8+ T cells had no statistical difference between these two groups. Cluster analysis showing that decrease of host immunity markers including CD3+, CD4+ and CD8+ T cells, and increase of tissue damage marker LDH were the most typical characteristics of PJP patients. A further established model based on combination of CD8+ T cells and LDH showed prominent value in distinguishing PJP from non-PJP, with AUC of 0.941 (95% CI, 0.892-0.990). Conclusions: A model based on combination of routine laboratory and immunological indicators shows prominent value for predicting the development of PJP in HIV-negative patients undergoing immunosuppressive therapy.
Asunto(s)
Biomarcadores , Huésped Inmunocomprometido , Infecciones Oportunistas , Pneumocystis carinii , Neumonía por Pneumocystis/diagnóstico , Neumonía por Pneumocystis/etiología , Adulto , Anciano , Biología Computacional/métodos , Susceptibilidad a Enfermedades , Femenino , Humanos , Inmunofenotipificación , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Pneumocystis carinii/inmunología , Pronóstico , Curva ROC , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
Pneumocystis jirovecii is one of the most common fungal pathogens in immunocompromised individuals. Pneumocystis jirovecii pneumonia (PJP) causes a significant host immune response that is driven greatly by the organism's cell wall components including ß-glucans and major surface glycoprotein (Msg). These ligands interact with a number of C-type lectin receptors (CLRs) leading to downstream activation of proinflammatory signaling pathways. This minireview provides a brief overview summarizing known CLR/Pneumocystis interactions.
Asunto(s)
Proteínas Fúngicas/inmunología , Inmunidad Innata , Lectinas Tipo C/inmunología , Glicoproteínas de Membrana/inmunología , Pneumocystis carinii/inmunología , Neumonía por Pneumocystis/inmunología , beta-Glucanos/inmunología , Animales , Proteínas Fúngicas/metabolismo , Interacciones Huésped-Patógeno , Humanos , Mediadores de Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Lectinas Tipo C/metabolismo , Ligandos , Glicoproteínas de Membrana/metabolismo , Pneumocystis carinii/metabolismo , Pneumocystis carinii/patogenicidad , Neumonía por Pneumocystis/metabolismo , Neumonía por Pneumocystis/microbiología , Transducción de Señal , beta-Glucanos/metabolismoRESUMEN
BACKGROUND: Pneumocystis pneumonia is a common opportunistic infection in kidney transplant recipients caused by the ascomycetous fungi Pneumocystis jirovecii. Its clinical presentation of a progressive nonproductive cough, shortness of breath, and fever is nonspecific and often delays diagnosis and appropriate treatment. Moreover, the plain radiograph may show a spectrum of findings from normal to bilateral diffuse infiltrates. Detection of serum (1,3)-ß-D-glucan along with consistent clinical findings can be used as early screening tools to diagnose and initiate treatment for Pneumocystis pneumonia pending confirmation by bronchoscopy. METHODS: This case series describes 6 kidney transplant recipients who were diagnosed as having Pneumocystis pneumonia. The baseline demographic variables, presenting symptoms, radiographic findings, laboratory findings including lactate dehydrogenase and serum (1,3)-ß-D-glucan levels, bronchoscopy findings, and its timing in relation to a positive serum (1,3)-ß-D-glucan test, and response to treatment were collected. RESULTS: All 6 patients who completed the first 3 months of prophylaxis against Pneumocystis pneumonia with sulfamethoxazole-trimethoprim were diagnosed as having Pneumocystis pneumonia between 2 to 24 years post transplant. They initiated treatment early based on a positive serum (1,3)-ß-D-glucan and negative Histoplasma antigen and serum galactomannan test with a presumptive diagnosis of Pneumocystis pneumonia, which was later confirmed with a positive polymerase chain reaction on bronchoalveolar lavage fluid. CONCLUSIONS: Pneumocystis pneumonia is a common opportunistic fungal infection in immunosuppressed kidney transplant recipients, and use of serum (1,3)-ß-D-glucan can be used as an initial screening test for its early diagnosis and treatment.
Asunto(s)
Trasplante de Riñón/efectos adversos , Infecciones Oportunistas/diagnóstico , Pneumocystis carinii/inmunología , Neumonía por Pneumocystis/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Proteoglicanos/sangre , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/microbiología , Neumonía por Pneumocystis/inmunología , Complicaciones Posoperatorias/microbiología , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: The human pathogen Pneumocystis jirovecii harbors 6 families of major surface glycoproteins (MSGs) encoded by a single gene superfamily. MSGs are presumably responsible for antigenic variation and adhesion to host cells. The genomic organization suggests that a single member of family I is expressed at a given time per cell, whereas members of the other families are simultaneously expressed. METHODS: We analyzed RNA sequences expressed in several clinical samples, using specific weighted profiles for sorting of reads and calling of single-nucleotide variants to estimate the diversity of the expressed genes. RESULTS: A number of different isoforms of at least 4 MSG families were expressed simultaneously, including isoforms of family I, for which confirmation was obtained in the wet laboratory. CONCLUSION: These observations suggest that every single P. jirovecii population is made of individual cells with distinct surface properties. Our results enhance our understanding of the unique antigenic variation system and cell surface structure of P. jirovecii.
Asunto(s)
Proteínas Fúngicas/genética , Regulación Fúngica de la Expresión Génica , Glicoproteínas de Membrana/genética , Pneumocystis carinii/genética , Neumonía por Pneumocystis/microbiología , Proteínas Fúngicas/inmunología , Variación Genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Glicoproteínas de Membrana/inmunología , Familia de Multigenes , Pneumocystis carinii/inmunología , Neumonía por Pneumocystis/inmunología , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: There is no consensus guidance on when to reinitiate Pneumocystis jirovecii pneumonia (PJP) prophylaxis in solid organ transplant (SOT) recipients at increased risk. The 2019 American Society of Transplantation Infectious Diseases Community of Practice (AST IDCOP) guidelines suggested to continue or reinstitute PJP prophylaxis in those receiving intensified immunosuppression for graft rejection, cytomegalovirus (CMV) infection, higher dose of corticosteroids, or prolonged neutropenia. METHODS: A literature search was conducted evaluating all literature from existence through April 22, 2020, using MEDLINE and EMBASE. (The International Prospective Register of Systematic Reviews registration number: CRD42019134204). RESULTS: A total of 30 studies with 413 276 SOT recipients were included. The following factors were associated with PJP development: acute rejection (pooled odds ratio [pOR], 2.35; 95% confidence interval [CI], 1.69-3.26); study heterogeneity index [I2] = 23.4%), CMV-related illnesses (pOR, 3.14; 95% CI, 2.30-4.29; I2 = 48%), absolute lymphocyte count <500 cells/mm3 (pOR, 6.29; 95% CI, 3.56-11.13; I2 = 0%), BK polyomavirus-related diseases (pOR, 2.59; 95% CI, 1.22-5.49; I2 = 0%), HLA mismatch ≥3 (pOR, 1.83; 95% CI, 1.06-3.17; I2 = 0%), rituximab use (pOR, 3.03; 95% CI, 1.82-5.04; I2 = 0%), and polyclonal antibodies use for rejection (pOR, 3.92; 95% CI, 1.87-8.19; I2 = 0%). On the other hand, sex, CMV mismatch, interleukin-2 inhibitors, corticosteroids for rejection, and plasmapheresis were not associated with developing PJP. CONCLUSIONS: PJP prophylaxis should be considered in SOT recipients with lymphopenia, BK polyomavirus-related infections, and rituximab exposure in addition to the previously mentioned risk factors in the American Society of Transplantation Infectious Diseases Community of Practice guidelines.
Asunto(s)
Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Infecciones Oportunistas/microbiología , Trasplante de Órganos/efectos adversos , Pneumocystis carinii/inmunología , Neumonía por Pneumocystis/microbiología , Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Femenino , Humanos , Masculino , Infecciones Oportunistas/inmunología , Infecciones Oportunistas/prevención & control , Pneumocystis carinii/efectos de los fármacos , Pneumocystis carinii/patogenicidad , Neumonía por Pneumocystis/inmunología , Neumonía por Pneumocystis/prevención & control , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Mannose-binding lectin (MBL) plays a pivotal role in innate immunity; however, its impact on susceptibility to opportunistic infections (OIs) has not yet been examined in a natural history cohort of people living with HIV/AIDS. METHODS: We used archived samples to analyze the association between MBL expression types and risk of major OIs including Pneumocystis jirovecii pneumonia (PCP), cryptococcosis, talaromycosis, toxoplasmosis, and tuberculosis in a prospective cohort in Northern Thailand conducted from 1 July 2000 to 15 October 2002 before the national antiretroviral treatment programme was launched. RESULTS: Of 632 patients, PCP was diagnosed in 96 (15.2%) patients, including 45 patients with new episodes during the follow-up period (1006.5 person-years). The total history of PCP was significantly associated with low MBL expression type: high/intermediate (81/587, 13.8%), low (10/33, 30.3%) and deficient (5/12, 41.7%) (p = 0.001), whereas the history of other OIs showed no relation with any MBL expression type. Kaplan-Meier analysis (n = 569; log-rank p = 0.011) and Cox's proportional hazards model revealed that deficient genotype dramatically increased the risk of PCP, which is independent upon sex, age, CD4 count, HIV-1 viral load and hepatitis B and C status (adjusted hazard ratio 7.93, 95% confidence interval 2.19-28.67, p = 0.002). CONCLUSIONS: Deficiency of MBL expression is a strong risk factor determining the incidence of PCP but not other major OIs.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Lectina de Unión a Manosa/deficiencia , Pneumocystis carinii/aislamiento & purificación , Neumonía por Pneumocystis/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/genética , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Técnicas de Genotipaje , Humanos , Inmunidad Innata/genética , Incidencia , Masculino , Lectina de Unión a Manosa/genética , Lectina de Unión a Manosa/inmunología , Persona de Mediana Edad , Pneumocystis carinii/inmunología , Neumonía por Pneumocystis/diagnóstico , Neumonía por Pneumocystis/genética , Neumonía por Pneumocystis/microbiología , Estudios Prospectivos , Factores de Riesgo , Tailandia/epidemiología , Adulto JovenRESUMEN
The Fungitell assay (FA) and the Wako ß-glucan test (GT) are employed to measure the serum/plasma 1,3-ß-D-glucan (BDG), a well-known invasive fungal disease biomarker. Data to convincingly and/or sufficiently support the GT as a valuable alternative to the FA are yet limited. In this study, we evaluated the FA and the GT to diagnose invasive aspergillosis (IA), invasive candidiasis (IC), and Pneumocystis jirovecii pneumonia (PJP). The FA and GT performances were compared in sera of patients with IA (n = 40), IC (n = 78), and PJP (n = 17) with respect to sera of control patients (n = 187). Using the manufacturer's cutoff values of 80 pg/mL and 11 pg/mL, the sensitivity and specificity for IA diagnosis were 92.5% and 99.5% for the FA and 60.0% and 99.5% for the GT, respectively; for IC diagnosis were 100.0% and 97.3% for the FA and 91.0% and 99.5% for the GT, respectively; for PJP diagnosis were 100.0% and 97.3% for the FA and 88.2% and 99.5% for the GT, respectively. When an optimized cutoff value of 7.0 pg/mL for the GT was used, the sensitivity and specificity were 80.0% and 97.3% for IA diagnosis, 98.7% and 97.3% for IC diagnosis, and 94.1% and 97.3% for PJP diagnosis, respectively. At the 7.0-pg/mL GT cutoff, the agreement between the assays remained and/or became excellent for IA (95.1%), IC (97.3%), and PJP (96.5%), respectively. In conclusion, we show that the GT performed as well as the FA only with a lowered cutoff value for positivity. Further studies are expected to establish the equivalence of the two BDG assays.
Asunto(s)
Aspergilosis/diagnóstico , Candidiasis Invasiva/diagnóstico , Pruebas Diagnósticas de Rutina/métodos , Neumonía por Pneumocystis/diagnóstico , beta-Glucanos/análisis , Adulto , Anciano , Aspergilosis/sangre , Aspergilosis/microbiología , Aspergillus/inmunología , Aspergillus/aislamiento & purificación , Candida albicans/inmunología , Candida albicans/aislamiento & purificación , Candidiasis Invasiva/sangre , Candidiasis Invasiva/microbiología , Pruebas Diagnósticas de Rutina/clasificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pneumocystis carinii/inmunología , Pneumocystis carinii/aislamiento & purificación , Neumonía por Pneumocystis/sangre , Neumonía por Pneumocystis/microbiología , Curva ROCRESUMEN
Caspase recruitment domains-containing protein 9 (CARD9) is an adaptor molecule critical for key signalling pathways initiated through C-type lectin receptors (CLRs). Previous studies demonstrated that Pneumocystis organisms are recognised through a variety of CLRs. However, the role of the downstream CARD9 adaptor signalling protein in host defence against Pneumocystis infection remains to be elucidated. Herein, we analysed the role of CARD9 in host defence against Pneumocystis both in CD4-depleted CARD9-/- and immunocompetent hosts. Card9 gene-disrupted (CARD9-/- ) mice were more susceptible to Pneumocystis, as evidenced by reduced fungal clearance in infected lungs compared to wild-type (WT) infected mice. Our data suggests that this defect was due to impaired proinflammatory responses. Furthermore, CARD9-/- macrophages were severely compromised in their ability to differentiate and express M1 and M2 macrophage polarisation markers, to enhanced mRNA expression for Dectin-1 and Mincle, and most importantly, to kill Pneumocystis in vitro. Remarkably, compared to WT mice, and despite markedly increased organism burdens, CARD9-/- animals did not exhibit worsened survival during pneumocystis pneumonia (PCP), perhaps related to decreased lung injury due to altered influx of inflammatory cells and decreased levels of proinflammatory cytokines in response to the organism. Finally, although innate phase cytokines were impaired in the CARD9-/- animals during PCP, T-helper cell cytokines were normal in immunocompetent CARD9-/- animals infected with Pneumocystis. Taken together, our data demonstrate that CARD9 has a critical function in innate immune responses against Pneumocystis.
Asunto(s)
Proteínas Adaptadoras de Señalización CARD/metabolismo , Macrófagos Alveolares/inmunología , Pneumocystis carinii/inmunología , Pneumocystis/inmunología , Neumonía por Pneumocystis/inmunología , Neumonía por Pneumocystis/metabolismo , Animales , Proteínas Adaptadoras de Señalización CARD/genética , Diferenciación Celular , Recuento de Colonia Microbiana , Citocinas/metabolismo , Huésped Inmunocomprometido , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Pulmón/enzimología , Pulmón/microbiología , Pulmón/patología , Macrófagos Alveolares/citología , Macrófagos Alveolares/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Peroxidasa/metabolismo , Pneumocystis/crecimiento & desarrollo , Pneumocystis carinii/crecimiento & desarrollo , Neumonía por Pneumocystis/microbiología , Neumonía por Pneumocystis/patología , Ratas , Linfocitos T Colaboradores-Inductores/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Interest in the detection of specific anti-Pneumocystis jirovecii antibodies has emerged as less-invasive alternative diagnostic approaches. Here is presented the performance of an ELISA based on a recombinant synthetic multi-epitope kexin 1 (Kex1) antigen of P. jirovecii, previously developed. Results showed that IgM anti-Kex1 levels were found significantly increased in patients with Pneumocystis pneumonia (PcP) compared with non-PcP cases (p < 0.001), allowing a diagnostic performance of PcP with a 70.8% sensitivity and a 75.0% specificity. These results suggest that this Kex1-based ELISA is a promising tool toward the serodiagnosis of PcP when the standard methods are difficult to perform.
Asunto(s)
Anticuerpos Antifúngicos/inmunología , Pneumocystis carinii/inmunología , Neumonía por Pneumocystis/microbiología , Área Bajo la Curva , Ensayo de Inmunoadsorción Enzimática , Humanos , Neumonía por Pneumocystis/sangre , Proproteína Convertasas/química , Proproteína Convertasas/inmunología , Estudios Retrospectivos , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/inmunología , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Pneumocystis major surface glycoprotein (Msg) is a 120-kD surface protein complex on the organism with importance in adhesion and immune recognition. In this study, we show that Msg significantly impairs tumor necrosis factor (TNF)-α secretion by macrophages induced by Saccharomyces cerevisiae and Pneumocystis carinii (Pc) ß-glucans. METHODS: Major surface glycoprotein was shown to greatly reduce ß-glucan-induced Dectin-1 immunoreceptor tyrosine-based activating motif (ITAM) phosphorylation. Major surface glycoprotein also down regulated Dectin-1 receptor messenger ribonucleic acid (mRNA) expression in the macrophages. It is interesting that Msg incubation with macrophages resulted in significant mRNA upregulation of both C-type lectin receptors (CLR) Mincle and MCL in Msg protein presence alone but to even greater amounts in the presence of Pc ß-glucan. RESULTS: The silencing of MCL and Mincle resulted in TNF-α secretions similar to that of macrophages treated with Pneumocystis ß-glucan alone, which is suggestive of an inhibitory role for these 2 CLRs in Msg-suppressive effects on host cell immune response. CONCLUSIONS: Taken together, these data indicate that the Pneumocystis Msg surface protein complex can act to suppress host macrophage inflammatory responses to the proinflammatory ß -glucan components of the organisms.
Asunto(s)
Lectinas Tipo C/metabolismo , Macrófagos/inmunología , Glicoproteínas de Membrana/metabolismo , Pneumocystis carinii/inmunología , Neumonía por Pneumocystis/inmunología , beta-Glucanos/metabolismo , Animales , Proteínas Fúngicas/metabolismo , Lectinas Tipo C/genética , Macrófagos/microbiología , Ratones , Pneumocystis/inmunología , Células RAW 264.7 , ARN Mensajero/genética , Saccharomyces cerevisiae/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , beta-Glucanos/inmunologíaAsunto(s)
Oxigenación por Membrana Extracorpórea , Trasplante de Riñón/efectos adversos , Neumonía por Pneumocystis/terapia , Insuficiencia Respiratoria/terapia , Adulto , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Masculino , Pneumocystis carinii/inmunología , Pneumocystis carinii/aislamiento & purificación , Neumonía por Pneumocystis/diagnóstico , Neumonía por Pneumocystis/inmunología , Neumonía por Pneumocystis/microbiología , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/inmunología , Insuficiencia Respiratoria/microbiología , Resultado del TratamientoAsunto(s)
Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Pneumocystis carinii/inmunología , Neumonía por Pneumocystis/inmunología , Neumonía Viral/inmunología , Proteínas Asociadas a Surfactante Pulmonar/química , Surfactantes Pulmonares/química , Glicoproteína de la Espiga del Coronavirus/química , Secuencia de Aminoácidos , Anticuerpos Antivirales/química , Anticuerpos Antivirales/genética , Betacoronavirus/patogenicidad , COVID-19 , Coronavirus Humano 229E/inmunología , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Coronavirus Humano OC43/inmunología , Reacciones Cruzadas , Epítopos/química , Epítopos/genética , Epítopos/inmunología , Expresión Génica , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Oligopéptidos/química , Oligopéptidos/genética , Oligopéptidos/inmunología , Pandemias , Pneumocystis carinii/patogenicidad , Neumonía por Pneumocystis/genética , Neumonía por Pneumocystis/patología , Neumonía por Pneumocystis/virología , Neumonía Viral/genética , Neumonía Viral/patología , Neumonía Viral/virología , Unión Proteica , Proteínas Asociadas a Surfactante Pulmonar/genética , Proteínas Asociadas a Surfactante Pulmonar/inmunología , Surfactantes Pulmonares/inmunología , Surfactantes Pulmonares/metabolismo , SARS-CoV-2 , Homología de Secuencia de Aminoácido , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
Most fungal species are harmless to humans and some exist as commensals on mucocutaneous surfaces. Yet many fungi are opportunistic pathogens, causing life-threatening invasive infections when the immune system becomes compromised. The fungal cell wall contains conserved pathogen-associated molecular patterns (PAMPs), which allow the immune system to distinguish between self (endogenous molecular patterns) and foreign material. Sensing of invasive microbial pathogens is achieved through recognition of PAMPs by pattern recognition receptors (PRRs). One of the predominant fungal-sensing PRRs is the C-type lectin receptor (CLR) family. These receptors bind to structures present on the fungal cell wall, eliciting various innate immune responses as well as shaping adaptive immunity. In this chapter, we specifically focus on the four major human fungal pathogens, Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans and Pneumocystis jirovecii, reviewing our current understanding of the CLRs that are involved in their recognition and protection of the host.
Asunto(s)
Hongos/inmunología , Inmunidad Innata/inmunología , Lectinas Tipo C/inmunología , Aspergillus fumigatus/inmunología , Candida albicans/inmunología , Cryptococcus neoformans/inmunología , Humanos , Moléculas de Patrón Molecular Asociado a Patógenos/inmunología , Pneumocystis carinii/inmunologíaRESUMEN
Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line agent for Pneumocystis jiroveci pneumonia (PJP) prophylaxis for solid organ transplant (SOT) recipients because of its efficacy for this indication, extended antimicrobial coverage, and favorable cost. Reported sulfonamide allergy is not uncommon and often results in TMP-SMX avoidance. Desensitization offers an efficacious and cost-effective alternative to TMP-SMX avoidance. Herein, we reviewed our experience with desensitization during the index transplant hospitalization among 52 SOT recipients with history of a non-anaphylactic sulfonamide allergy. Of those enrolled in the desensitization protocol, 92% (48/52) completed the protocol, with nearly 80% (41/52) still on TMP-SMX at 3 months without adverse reaction. Eleven patients discontinued TMP-SMX (7 for allergic reactions and 4 for non-allergic reasons) and switched to pentamidine. A cost savings of $575 per desensitization was calculated based on annual wholesale drug prices, for a total savings of $23 575. Additionally, the protocol did not delay discharge in any patient nor was it associated with any severe allergic reactions. These findings suggest TMP-SMX desensitization is safe and effective in SOT recipients with a history of non-anaphylactic, non-life-threatening sulfonamide hypersensitivity.
Asunto(s)
Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/terapia , Trasplante de Órganos/efectos adversos , Neumonía por Pneumocystis/prevención & control , Combinación Trimetoprim y Sulfametoxazol/inmunología , Ahorro de Costo , Desensibilización Inmunológica/efectos adversos , Desensibilización Inmunológica/economía , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/inmunología , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pneumocystis carinii/inmunología , Pneumocystis carinii/aislamiento & purificación , Neumonía por Pneumocystis/inmunología , Neumonía por Pneumocystis/microbiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Receptores de Trasplantes , Combinación Trimetoprim y Sulfametoxazol/administración & dosificación , Combinación Trimetoprim y Sulfametoxazol/economíaRESUMEN
INTRODUCTION: The incidence of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients after an episode of Pneumocystis jirovecii pneumonia (PJP) seems to be lower than with other opportunistic infections. We conducted an observational study in order to determine the incidence, clinical characteristics and outcome of patients diagnosed with PJP-related IRIS. METHODS: We conducted an observational study of HIV patients diagnosed with PJP-related IRIS from January 2000 to November 2015. We analyzed epidemiological and clinical characteristics as well as laboratory findings. We also carried out a systematic review of published cases. RESULTS: Six cases of IRIS out of 123 (4.9%) HIV-infected patients with PJP who started ART were diagnosed. All six cases were men with a median age of 34 (IQR: 8) years. The six patients developed paradoxical IRIS. Subjects younger than 40 years old (p = 0.084) and with an HIV-RNA viral load >100000 copies/ml (p = 0.081) at diagnosis showed a tendency to develop IRIS. Thirty-seven published cases of PJP-related IRIS were identified. Although 51% of cases involved respiratory failure, no deaths were reported. CONCLUSIONS: PJP-related IRIS is rare condition compared to other opportunistic infections. It can lead to a severe respiratory failure in a significant proportion of cases, although no deaths have been reported
INTRODUCCIÓN: La incidencia del síndrome inflamatorio de reconstitución inmune (SIRI) en pacientes infectados por el virus de la inmunodeficiencia humana (VIH) después de un episodio de neumonía por Pneumocystis jirovecii (PJP) parece ser menor que con otras infecciones oportunistas. Hemos realizado un estudio observacional con el objetivo de conocer la incidencia, las características clínicas y la evolución de los pacientes diagnosticados de SIRI asociado con la PJP. MÉTODOS: Se ha realizado un estudio observacional de pacientes con VIH diagnosticados de SIRI asociado a PJP desde enero del 2000 hasta noviembre de 2015. Fueron analizadas características epidemiológicas y clínicas, así como hallazgos de laboratorio. Asimismo, se ha llevado a cabo una revisión sistemática de los casos publicados previamente. RESULTADOS: Se identificaron 6 casos de SIRI en 123 pacientes con VIH (4,9%) con PJP que comenzaron TAR. Los 6 casos eran varones con una edad media de 34 (IQR :8) años. En los 6 casos se trató de una SIRI paradójico. Los sujetos menores de 40 años (p = 0,084) y con VIH-ARN al diagnóstico mayor de 100.000 copias/ml (p = 0,081) mostraron una tendencia a desarrollar SIRI. Se identificaron 37 casos publicados de SIRI relacionado con PJP en la literatura. Aunque el 51% de los casos presentaron insuficiencia respiratoria, no se reportaron muertes. CONCLUSIONES: El SIRI asociado con PJP es una entidad infrecuente comparada con el relacionado con otras infecciones oportunistas. Puede provocar insuficiencia respiratoria grave en un porcentaje importante de casos, si bien no se han reportado muertes
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Pneumocystis carinii/inmunología , Infecciones por Pneumocystis/epidemiología , Síndrome Inflamatorio de Reconstitución Inmune/epidemiología , Síndrome Inflamatorio de Reconstitución Inmune/inmunología , Incidencia , España/epidemiología , Estudio Observacional , Estudios RetrospectivosRESUMEN
Although Pneumocystis jiroveci pneumonia (PCP) is a frequent manifestation of acquired immune deficiency syndrome (AIDS), the granulomatous form is uncommon. Here, we present an unusual case of granulomatous PCP consequent to immune reconstitution inflammatory syndrome (IRIS) after highly active antiretroviral therapy. A 36-year-old woman with human immunodeficiency virus (HIV) presented with cough and dyspnea that were attributed to typical PCP associated with AIDS. She was successfully treated with antibiotic, steroid, and antiretroviral therapies. After six months, however, she presented with consolidating lung lesions caused by bronchial obstruction from PCP granulomatous disease. Although antibiotics were ineffective, the effectiveness of steroid therapy suggested a diagnosis of granulomatous IRIS caused by persistent PCP antigens. Physicians should strongly suspect PCP in HIV-positive patients with nodular lung lesions and must remain aware that these lesions, if immune in origin, might not respond to antimicrobial therapy.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Granuloma del Sistema Respiratorio/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Síndrome Inflamatorio de Reconstitución Inmune/complicaciones , Pulmón/diagnóstico por imagen , Pneumocystis carinii/aislamiento & purificación , Neumonía por Pneumocystis/diagnóstico , Adulto , Antiinfecciosos Urinarios/uso terapéutico , Broncoscopía , Femenino , Granuloma del Sistema Respiratorio/complicaciones , Infecciones por VIH/complicaciones , Infecciones por VIH/microbiología , Humanos , Síndrome Inflamatorio de Reconstitución Inmune/tratamiento farmacológico , Huésped Inmunocomprometido , Pneumocystis carinii/inmunología , Neumonía por Pneumocystis/tratamiento farmacológico , Prednisona/uso terapéutico , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Combinación Trimetoprim y SulfametoxazolRESUMEN
Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection diagnosed in immunocompromized patients. After solid organ transplantation, early infection has decreased as a result of effective prophylaxis, but late infections and even outbreaks caused by interpatient transmission of pneumocystis by air are present in the SOT community. Different risk factors for PJP have been described and several indications for PJP prophylaxis have to be considered by clinicians in patients even years after transplantation. Diagnosis of PJP is confirmed by microscopy and immunofluorescence staining of bronchial fluid but PCR as well as serum ß-D-Glucan analysis have become increasingly valuable diagnostic tools. Treatment of choice is Trimethoprim/sulfamethoxazole and early treatment improves prognosis. However, mortality of PJP in solid organ transplant patients is still high and many aspects including the optimal management of immunosuppression during PJP treatment require further investigations.