RESUMO
The role of the microbiome in asthma is highlighted, considering its influence on immune responses and its connection to alterations in asthmatic patients. In this context, we review the variables influencing asthma phenotypes from a microbiome perspective and provide insights into the microbiome's role in asthma pathogenesis. Previous cohort studies in patients with asthma have shown that the presence of genera such as Bifidobacterium, Lactobacillus, Faecalibacterium, and Bacteroides in the gut microbiome has been associated with protection against the disease. While, the presence of other genera such as Haemophilus, Streptococcus, Staphylococcus, and Moraxella in the respiratory microbiome has been implicated in asthma pathogenesis, indicating a potential link between microbial dysbiosis and the development of asthma. Furthermore, respiratory infections have been demonstrated to impact the composition of the upper respiratory tract microbiota, increasing susceptibility to bacterial diseases and potentially triggering asthma exacerbations. By understanding the interplay between the microbiome and asthma, valuable insights into disease mechanisms can be gained, potentially leading to the development of novel therapeutic approaches.
RESUMO
Background: The SARS-CoV-2 virus has caused unprecedented mortality since its emergence in late 2019. The continuous evolution of the viral genome through the concerted action of mutational forces has produced distinct variants that became dominant, challenging human immunity and vaccine development. Aim and methods: In this work, through an integrative genomic approach, we describe the molecular transition of SARS-CoV-2 by analyzing the viral whole genome sequences from 50 critical COVID-19 patients recruited during the first year of the pandemic in Mexico City. Results: Our results revealed differential levels of the evolutionary forces across the genome and specific mutational processes that have shaped the first two epidemiological waves of the pandemic in Mexico. Through phylogenetic analyses, we observed a genomic transition in the circulating SARS-CoV-2 genomes from several lineages prevalent in the first wave to a dominance of the B.1.1.519 variant (defined by T478K, P681H, and T732A mutations in the spike protein) in the second wave. Conclusion: This work contributes to a better understanding of the evolutionary dynamics and selective pressures that act at the genomic level, the prediction of more accurate variants of clinical significance, and a better comprehension of the molecular mechanisms driving the evolution of SARS-CoV-2 to improve vaccine and drug development.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , Pandemias , México/epidemiologia , Filogenia , Genoma Viral , MutaçãoRESUMO
OBJECTIVES: SSc is a devastating autoimmune disease characterized by fibrosis and obliterative vasculopathy affecting the skin and visceral organs. While the processes mediating excessive extracellular matrix deposition and fibroblast proliferation are clear, the exact link between autoimmunity and fibrosis remains elusive. Th17 cells have been proposed as critical drivers of profibrotic inflammation during SSc, but little is known about the immune components supporting their pathogenic role. Our aim was to determine cytokine responses of stimulated monocyte-derived dendritic cells (Mo-DCs) and to determine how they influence T-cell cytokine production in SSc. MATERIAL AND METHODS: Dendritic cells (DCs) activate and shape T cell differentiation by producing polarizing cytokines. Hence, we investigated the cytokine responses of monocyte-derived DCs (Mo-DCs) from patients with limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc) and healthy controls (HCs) after stimulation with toll-like receptor (TLR) agonists. Also, using co-culture assays, we analysed T cell subpopulations after contact with autologous TLR-activated Mo-DCs. RESULTS: In general, we observed an increased production of Th17-related cytokines like IL-1ß, IL-17F, IL-21 and IL-22 by SSc compared with HC Mo-DCs, with variations between lcSSc vs dcSSc and early- vs late-stage subgroups. Noticeably, we found a significant increment in IL-33 production by Mo-DCs in all SSc cases regardless of their clinical phenotype. Strikingly, T cells displayed Th2, Th17 and dual Th2-Th17 phenotypes after exposure to autologous TLR-stimulated Mo-DCs from SSc patients but not HCs. These changes were pronounced in individuals with early-stage dcSSc and less significant in the late-stage lcSSc subgroup. CONCLUSIONS: Our findings suggest that functional alterations of DCs promote immune mechanisms favouring the aberrant T cell polarization and profibrotic inflammation behind clinical SSc heterogeneity.
Assuntos
Escleroderma Sistêmico , Humanos , Citocinas , Fibrose , Células Dendríticas/patologia , InflamaçãoRESUMO
Interferon-induced transmembrane (IFITM) proteins mediate protection against enveloped viruses by blocking membrane fusion at endosomes. IFITM1 and IFITM3 are crucial for protection against influenza, and various single nucleotide polymorphisms altering their function have been linked to disease susceptibility. However, bulk IFITM1 and IFITM3 mRNA expression dynamics and their correlation with clinical outcomes have not been extensively addressed in patients with respiratory infections. In this study, we evaluated the expression of IFITM1 and IFITM3 in peripheral leukocytes from healthy controls and individuals with severe pandemic influenza A(H1N1) or coronavirus disease 2019 (COVID-19). Comparisons between participants grouped according to their clinical characteristics, underlying disease, and outcomes showed that the downregulation of IFITM1 was a distinctive characteristic of severe pandemic influenza A(H1N1) that correlated with outcomes, including mortality. Conversely, increased IFITM3 expression was a common feature of severe pandemic influenza A(H1N1) and COVID-19. Using a high-dose murine model of infection, we confirmed not only the downregulation of IFITM1 but also of IFITM3 in the lungs of mice with severe influenza, as opposed to humans. Analyses in the comparative cohort also indicate the possible participation of IFITM3 in COVID-19. Our results add to the evidence supporting a protective function of IFITM proteins against viral respiratory infections in humans.
Assuntos
Antígenos de Diferenciação , COVID-19 , Influenza Humana , Proteínas de Membrana , Proteínas de Ligação a RNA , Animais , Antígenos de Diferenciação/genética , Antígenos de Diferenciação/metabolismo , COVID-19/genética , Humanos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/genética , Leucócitos/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
The costs of coronavirus disease 2019 (COVID-19) are devastating. With millions of deaths worldwide, specific serological biomarkers, antiviral agents, and novel therapies are urgently required to reduce the disease burden. For these purposes, a profound understanding of the pathobiology of COVID-19 is mandatory. Notably, the study of immunity against other respiratory infections has generated reference knowledge to comprehend the paradox of the COVID-19 pathogenesis. Past studies point to a complex interplay between cytokines and other factors mediating wound healing and extracellular matrix (ECM) remodeling that results in exacerbated inflammation, tissue injury, severe manifestations, and a sequela of respiratory infections. This review provides an overview of the immunological process elicited after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Also, we analyzed available data about the participation of matrix metalloproteinases (MMPs) and transforming growth factor-beta (TGF-ß) in immune responses of the lungs. Furthermore, we discuss their possible implications in severe COVID-19 and sequela, including pulmonary fibrosis, and remark on the potential of these molecules as biomarkers for diagnosis, prognosis, and treatment of convalescent COVID-19 patients. Our review provides a theoretical framework for future research aimed to discover molecular hallmarks that, combined with clinical features, could serve as therapeutic targets and reliable biomarkers of the different clinical forms of COVID-19, including convalescence.
Assuntos
COVID-19 , Metaloproteinases da Matriz , Fator de Crescimento Transformador beta , Biomarcadores , COVID-19/imunologia , Efeitos Psicossociais da Doença , Humanos , Metaloproteinases da Matriz/imunologia , SARS-CoV-2 , Fator de Crescimento Transformador beta/imunologiaRESUMO
CXCL17 is a novel mucosal chemokine that mediates myeloid cell recruitment and bactericidal activity and highly expressed in the respiratory tract. However, its role in tuberculosis (TB) immunopathogenesis or protection remains unknown. In this study, we evaluated the function of CXCL17 in a mouse model of aerosol infection with the clinical W-Beijing lineage Mycobacterium tuberculosis hypervirulent HN878 strain. Our results show that CXCL17 production increases in the lung of M. tuberculosis-infected mice during acute and chronic stages of infection. Moreover, in vitro M. tuberculosis infection of epithelial cells and myeloid cells induces production of CXCL17. In humans, lower serum CXCL17 levels are observed among active pulmonary TB patients when compared with subjects with latent TB infection and healthy controls, suggesting a protective role. However, mice treated with rCXCL17 show similar lung bacterial burden and inflammation compared with control animals, despite an increased lung myeloid cell accumulation. Finally, CXCL17-/- mice are not more susceptible to TB than wild-type animals. These findings suggest that CXCL17 is induced in both murine epithelial and myeloid cells upon M. tuberculosis infection and increased expression during human latent TB infection. However, CXCL17 may have a dispensable role during pulmonary TB.
Assuntos
Quimiocinas CXC/metabolismo , Tuberculose Latente/imunologia , Pulmão/patologia , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Animais , Estudos de Casos e Controles , Quimiocinas CXC/administração & dosagem , Quimiocinas CXC/genética , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Voluntários Saudáveis , Humanos , Exposição por Inalação/efeitos adversos , Tuberculose Latente/sangue , Tuberculose Latente/diagnóstico , Tuberculose Latente/microbiologia , Pulmão/diagnóstico por imagem , Pulmão/imunologia , Pulmão/microbiologia , Camundongos , Camundongos Knockout , Mycobacterium tuberculosis/patogenicidade , Células Mieloides/imunologia , Células Mieloides/metabolismo , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologiaRESUMO
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1ß, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic.
Assuntos
COVID-19 , Citocinas , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Metaloproteinase 1 da Matriz , Metaloproteinase 3 da Matriz , Receptores Imunológicos , Adulto , Idoso , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/imunologia , Citocinas/sangue , Citocinas/imunologia , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/metabolismo , Influenza Humana/sangue , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Masculino , Metaloproteinase 1 da Matriz/sangue , Metaloproteinase 1 da Matriz/imunologia , Metaloproteinase 3 da Matriz/sangue , Metaloproteinase 3 da Matriz/imunologia , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores Imunológicos/sangue , Receptores Imunológicos/imunologia , Células Th1/imunologia , Células Th2/imunologiaRESUMO
[This corrects the article DOI: 10.3389/fimmu.2021.633297.].
RESUMO
The mechanisms underlying the immunopathology of tuberculous meningitis (TBM), the most severe clinical form of extrapulmonary tuberculosis (TB), are not understood. It is currently believed that the spread of Mycobacterium tuberculosis (Mtb) from the lung is an early event that occurs before the establishment of adaptive immunity. Hence, several innate immune mechanisms may participate in the containment of Mtb infection and prevent extrapulmonary disease manifestations. Natural killer (NK) cells participate in defensive processes that distinguish latent TB infection (LTBI) from active pulmonary TB (PTB). However, their role in TBM is unknown. Here, we performed a cross-sectional analysis of circulating NK cellCID="C008" value="s" phenotype in a prospective cohort of TBM patients (n = 10) using flow cytometry. Also, we addressed the responses of memory-like NK cell subpopulations to the contact with Mtb antigens in vitro. Finally, we determined plasma levels of soluble NKG2D receptor ligands in our cohort of TBM patients by enzyme-linked immunosorbent assay (ELISA). Our comparative groups consisted of individuals with LTBI (n = 11) and PTB (n = 27) patients. We found that NK cells from TBM patients showed lower absolute frequencies, higher CD69 expression, and poor expansion of the CD45RO+ memory-like subpopulation upon Mtb exposure in vitro compared to LTBI individuals. In addition, a reduction in the frequency of CD56brightCD16- NK cells characterized TBM patients but not LTBI or PTB subjects. Our study expands on earlier reports about the role of NK cells in TBM showing a reduced frequency of cytokine-producing cells compared to LTBI and PTB.
Assuntos
Células Matadoras Naturais/imunologia , Tuberculose Latente/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose Meníngea/imunologia , Tuberculose Pulmonar/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Citocinas/metabolismo , Feminino , Humanos , Imunidade Inata , Imunofenotipagem , Células Matadoras Naturais/metabolismo , Tuberculose Latente/sangue , Tuberculose Latente/microbiologia , Masculino , México , Pessoa de Meia-Idade , Estudos Prospectivos , Tuberculose Meníngea/sangue , Tuberculose Meníngea/microbiologia , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/microbiologia , Adulto JovemRESUMO
The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.
Assuntos
Biomarcadores/metabolismo , Quimiocinas CXC/metabolismo , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/diagnóstico , Pulmão/metabolismo , Mycobacterium tuberculosis/fisiologia , SARS-CoV-2/fisiologia , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/mortalidade , Quimiocinas CXC/genética , Quimiocinas CXC/imunologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Influenza Humana/mortalidade , Pulmão/patologia , Masculino , México , Pessoa de Meia-Idade , Pandemias , Avaliação de Resultados da Assistência ao Paciente , Prognóstico , Análise de Sobrevida , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/mortalidade , Adulto JovemRESUMO
The differentiation between influenza and coronavirus disease 2019 (COVID-19) could constitute a diagnostic challenge during the ongoing winter owing to their clinical similitude. Thus, novel biomarkers are required to enable making this distinction. Here, we evaluated whether the surfactant protein D (SP-D), a collectin produced at the alveolar epithelium with known immune properties, was useful to differentiate pandemic influenza A(H1N1) from COVID-19 in critically ill patients. Our results revealed high serum SP-D levels in patients with severe pandemic influenza but not those with COVID-19. This finding was validated in a separate cohort of mechanically ventilated patients with COVID-19 who also showed low plasma SP-D levels. However, plasma SP-D levels did not distinguish seasonal influenza from COVID-19 in mild-to-moderate disease. Finally, we found that high serum SP-D levels were associated with death and renal failure among severe pandemic influenza cases. Thus, our studies have identified SP-D as a unique biomarker expressed during severe pandemic influenza but not COVID-19.
Assuntos
COVID-19/genética , Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/genética , Proteína D Associada a Surfactante Pulmonar/genética , SARS-CoV-2 , Adulto , Idoso , Biomarcadores , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/virologia , Coinfecção , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Influenza Humana/diagnóstico , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteína D Associada a Surfactante Pulmonar/sangue , Índice de Gravidade de Doença , Avaliação de Sintomas , Adulto JovemRESUMO
Natural killer (NK) cells participate in immunity against several pathogens by exerting cytotoxic and cytokine-production activities. Some NK cell subsets also mediate recall responses that resemble memory of adaptive lymphocytes against antigenic and non-antigenic stimuli. The C-X-C motif chemokine receptor 6 (CXCR6) is crucial for the development and maintenance of memory-like responses in murine NK cells. In humans, several subsets of tissue-resident and circulating NK cells with different functional properties express CXCR6. However, the role of CXCR6+ NK cells in immunity against relevant human pathogens is unknown. Here, we addressed whether murine and human CXCR6+ NK cells respond to antigens of Mycobacterium tuberculosis (Mtb). For this purpose, we evaluated the immunophenotype of hepatic and splenic CXCR6+ NK cells in mice exposed to a cell-wall (CW) extract of Mtb strain H37Rv. Also, we characterized the expression of CXCR6 in peripheral NK cells from active pulmonary tuberculosis (ATB) patients, individuals with latent TB infection (LTBI), and healthy volunteer donors (HD). Furthermore, we evaluated the responses of CXCR6+ NK cells from HD, LTBI, and ATB subjects to the in vitro exposure to CW preparations of Mtb H37Rv and Mtb HN878. Our results showed that murine hepatic CXCR6+ NK cells expand in vivo after consecutive administrations of Mtb H37Rv CW to mice. Remarkably, pooled hepatic and splenic, but not isolated splenic NK cells from treated mice, enhance their cytokine production capacity after an in vitro re-challenge with H37Rv CW. In humans, CXCR6+ NK cells were barely detected in the peripheral blood, although slightly significative increments in the percentage of CXCR6+, CXCR6+CD49a-, CXCR6+CD49a+, and CXCR6+CD69+ NK cells were observed in ATB patients as compared to HD and LTBI individuals. In contrast, the expansion of CXCR6+CD49a- and CXCR6+CD69+ NK cells in response to the in vitro stimulation with Mtb H37Rv was higher in LTBI individuals than in ATB patients. Finally, we found that Mtb HN878 CW generates IFN-γ-producing CXCR6+CD49a+ NK cells. Our results demonstrate that antigens of both laboratory-adapted and clinical Mtb strains are stimulating factors for murine and human CXCR6+ NK cells. Future studies evaluating the role of CXCR6+ NK cells during TB are warranted.
Assuntos
Antígenos de Bactérias/imunologia , Células Matadoras Naturais/imunologia , Tuberculose Latente/imunologia , Mycobacterium tuberculosis/fisiologia , Tuberculose Pulmonar/imunologia , Animais , Células Cultivadas , Feminino , Humanos , Imunofenotipagem , Interferon gama/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Receptores CXCR6/metabolismoRESUMO
Here we studied HLA blocks and haplotypes in a group of 218 Lacandon Maya Native American using a high-resolution next generation sequencing (NGS) method. We assessed the genetic diversity of HLA class I and class II in this population, and determined the most probable ancestry of Lacandon Maya HLA class I and class II haplotypes. Importantly, this Native American group showed a high degree of both HLA homozygosity and linkage disequilibrium across the HLA region and also lower class II HLA allelic diversity than most previously reported populations (including other Native American groups). Distinctive alleles present in the Lacandon population include HLA-A*24:14 and HLA-B*40:08. Furthermore, in Lacandons we observed a high frequency of haplotypes containing the allele HLA-DRB1*04:11, a relatively frequent allele in comparison with other neighboring indigenous groups. The specific demographic history of the Lacandon population including inbreeding, as well as pathogen selection, may have elevated the frequencies of a small number of HLA class II alleles and DNA blocks. To assess the possible role of different selective pressures in determining Native American HLA diversity, we evaluated the relationship between genetic diversity at HLA-A, HLA-B and HLA-DRB1 and pathogen richness for a global dataset and for Native American populations alone. In keeping with previous studies of such relationships we included distance from Africa as a covariate. After correction for multiple comparisons we did not find any significant relationship between pathogen diversity and HLA genetic diversity (as measured by polymorphism information content) in either our global dataset or the Native American subset of the dataset. We found the expected negative relationship between genetic diversity and distance from Africa in the global dataset, but no relationship between HLA genetic diversity and distance from Africa when Native American populations were considered alone.
Assuntos
Variação Genética , Genética Populacional , Haplótipos , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe I/genética , Desequilíbrio de Ligação , Adolescente , Adulto , África , Alelos , Feminino , Frequência do Gene , Genótipo , Geografia , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cadeias HLA-DRB1/genética , Homozigoto , Humanos , Masculino , México/etnologia , Pessoa de Meia-Idade , Análise de Componente Principal , Adulto Jovem , Indígena Americano ou Nativo do AlascaRESUMO
OBJECTIVES: To describe the kinetics of circulating cytokines and chemokines in humans with ZIKAV infection. METHODS: Serum levels of different immune mediators in patients with ZIKAV infection were measured at distinct stages of the disease, as well as in culture supernatants from human monocytes infected with a clinical ZIKAV isolate. We also looked for clinical features associated with specific immune signatures among symptomatic patients. RESULTS: We evaluated 23 ZIKAV-infected patients. Their mean age was 32 ± 8.3 years and 65% were female. ZIKAV patients showed elevated IL-9, IL-17A, and CXCL10 levels at acute stages of the disease. At day 28, levels of CCL4 and CCL5 were increased, whereas IL-1RA, CXCL8 and CCL2 were decreased. At baseline, IL-7 was increased among patients with headache, whereas CCL2, and CCL3 were decreased in patients with bleeding and rash, respectively. Our clinical ZIKAV isolate induced a broad immune response in monocytes that did not resemble the signature observed in ZIKAV patients. CONCLUSIONS: We showed a unique immune signature in our cohort of ZIKAV-infected patients. Our study may provide valuable evidence helpful to identify immune correlates of protection against ZIKAV.
Assuntos
Quimiocinas/sangue , Citocinas/sangue , Infecção por Zika virus/imunologia , Zika virus/imunologia , Adulto , Estudos de Coortes , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/sangue , Interleucina-8/sangue , Masculino , México , Infecção por Zika virus/sangue , Infecção por Zika virus/virologiaRESUMO
OBJECTIVES: To evaluate the performance of rapid influenza diagnostic tests (RIDT) and influenza vaccines' effectiveness (VE) during an outbreak setting. METHODS: We compared the performance of a RIDT with RT-PCR for influenza virus detection in influenza-like illness (ILI) patients enrolled during the 2016/17 season in Mexico City. Using the test-negative design, we estimated influenza VE in all participants and stratified by age, virus subtype, and vaccine type (trivalent vs quadrivalent inactivated vaccines). The protective value of some clinical variables was evaluated by regression analyses. RESULTS: We enrolled 592 patients. RT-PCR detected 93 cases of influenza A(H1N1)pdm09, 55 of AH3N2, 141 of B, and 13 A/B virus infections. RIDT showed 90.7% sensitivity and 95.7% specificity for influenza A virus detection, and 91.5% sensitivity and 95.3% specificity for influenza B virus detection. Overall VE was 33.2% (95% CI: 3.0-54.0; p = 0.02) against any laboratory-confirmed influenza infection. VE estimates against influenza B were higher for the quadrivalent vaccine. Immunization and occupational exposure were protective factors against influenza. CONCLUSIONS: The RIDT was useful to detect influenza cases during an outbreak setting. Effectiveness of 2016/17 influenza vaccines administered in Mexico was low but significant. Our data should be considered for future local epidemiological policies.
Assuntos
Vacinas contra Influenza/administração & dosagem , Influenza Humana/diagnóstico , Adolescente , Adulto , Criança , Testes Diagnósticos de Rotina/métodos , Surtos de Doenças , Feminino , Humanos , Imunização , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza B/genética , Vírus da Influenza B/imunologia , Vírus da Influenza B/isolamento & purificação , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Estações do Ano , Vacinação , Adulto JovemRESUMO
BACKGROUND: The role of miRNAs in the pathogenesis of cutaneous lupus has not been studied. OBJECTIVE: It was to assess the levels of a selected panel of circulating miRNAs that could be involved in the regulation of the immune response, inflammation, and fibrosis in cutaneous lupus. METHODS: It was a cross-sectional study. We included 22 patients with subacute (SCLE) and 20 with discoid (DLE) lesions, and 19 healthy donors (HD). qRT-PCR for miRNA analysis, flow cytometry in peripheral blood, and skin immunohistochemistry were performed to determine the distribution of CD4 T cells and regulatory cells and their correlation with circulating miRNAs. RESULTS: miR-150, miR-1246, miR-21, miR-23b, and miR-146 levels were downregulated in SCLE vs. HD. miR-150, miR-1246, and miR-21 levels were downregulated in DLE vs. HD. miR-150, miR-1246, and miR-21 levels were downregulated in DLE γ + with miR-1246 in SCLE, whereas CD123+/CD196+/IDO+ cells were positively associated with miR-150 in DLE. In the tissue, CD4+/IL-4+ and CD20+/IL-10+ cells were positively associated with miR-21 and CD4+/IFN-γ + with miR-1246 in SCLE, whereas CD123+/CD196+/IDO+ cells were positively associated with miR-150 in DLE. In the tissue, CD4+/IL-4+ and CD20+/IL-10+ cells were positively associated with miR-21 and CD4+/IFN-ß, thyroid hormone, and cancer signaling pathways were shared between miR-21, miR-31, miR-23b, miR-146a, miR-1246, and miR-150. CONCLUSIONS: A downregulation of miR-150, miR-1246, and miR-21 in both CLE varieties vs. HD. miR-150, miR-1246, and miR-21 levels were downregulated in DLE.
Assuntos
Lúpus Eritematoso Cutâneo/metabolismo , Lúpus Eritematoso Cutâneo/patologia , MicroRNAs/metabolismo , Adulto , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Leucócitos Mononucleares/metabolismo , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Pele/metabolismo , Pele/patologiaRESUMO
Idiopathic achalasia is a relatively infrequent esophageal motor disorder for which major histocompatibility complex (MHC) genes are well-identified risk factors. However, no information about HLA-achalasia susceptibility in Mexicans has previously been reported. We studied a group of 91 patients diagnosed with achalasia and 234 healthy controls with Mexican admixed ancestry. HLA alleles and conserved extended haplotypes were analyzed using high-resolution HLA typing based on Sanger and next-generation sequencing technologies. Admixture estimates were determined using HLA-B and short tandem repeats. Results were analyzed by non-parametric statistical analysis and Bonferroni correction. P-values < 0.05 were considered significant. Patients with achalasia had 56.7% Native American genes, 24.7% European genes, 16.5% African genes and 2.0% Asian genes, which was comparable with the estimates in the controls. Significant increases in the frequencies of alleles DRB1*14:54 and DQB1*05:03 and the extended haplotypes DRB1*14:54-DQB1*05:03 and DRB1*11:01-DQB1*03:01, even after Bonferroni correction (pC<0.05), were found in the achalasia group compared to those in the controls. Concluding, the HLA class II alleles HLA-DRB1*14:54:01 and DQB1*05:03:01 and the extended haplotype are risk factors for achalasia in mixed-ancestry Mexican individuals. These results also suggest that the HLA-DRB1*14:54-DQB1*05:03 haplotype was introduced by admixture with European and/or Asian populations.
Assuntos
Acalasia Esofágica/genética , Etnicidade/genética , Predisposição Genética para Doença , Genética Populacional , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Haplótipos , Adulto , Estudos de Casos e Controles , Acalasia Esofágica/epidemiologia , Feminino , Variação Genética , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-IdadeRESUMO
In Chagas disease the clinical, acute and chronic manifestations are the result of the interaction between the parasite and the host factors. The balance between inflammatory and anti-inflammatory immune responses is essential for the increase or resolution of the manifestations in individuals infected with T. cruzi. To identify if children with chronic Chagas disease and heart injury is related with non-regulated Th1, Th2 and Th17 responses. We included 31 children with T. cruzi confirmed chronic infection from endemic areas of Mexico. Subsequently, they were separated according to their ECHO and ECG results into three groups according to the severity of cardiac involvement. Circulating Th1, Th2 and Th17 cytokine profiles were performed by Luminex assays and the results were analyzed by bivariate and multivariable analysis. Patients were classified in asymptomatic chronic (group 1, N=12); individuals with IRBBB in ECG and incipient lesions in ECHO (Group 2, N=8) and Patients with severe chronic symptomatic disease (Group 3, N=11). The analysis of immune mediators revealed that patients with severe cardiac manifestations had significant higher levels (p <0.05) of Th17 related cytokines including IL-17 and IL-6 as well as IFN-γ and IL-2. Also patients with severe cardiomyopathy exhibit increased levels of IL-13 (p <0.05) after multivariate analysis. High levels of Th17 related cytokines including IL-17, IFN-γ, IL-6 and IL-2 and pro-fibrotic factors such as IL-13 could be associated to the severity of cardiac involvement in children with chronic T. cruzi infection. These cytokines could be useful as indicators for the early identification of cardiac damage associated to the T. cruzi infection.
Assuntos
Doença de Chagas/epidemiologia , Doença de Chagas/patologia , Citocinas/sangue , Doenças Endêmicas , Trypanosoma cruzi/imunologia , Animais , Biomarcadores/sangue , Doença de Chagas/sangue , Doença de Chagas/parasitologia , Criança , Feminino , Humanos , Masculino , México/epidemiologiaRESUMO
Natural killer (NK) cells are lymphocytes of the innate immune system, which play an important role in the initial defense against a wide variety of pathogens, including viruses and intracellular bacteria. NK cells produce cytokines that enhance immune responses directed toward pathogens and also exert cytotoxic activity against infected cells, thereby eliminating the reservoir of infection. Their role in defense against Mycobacterium tuberculosis (Mtb) has been recently studied, and there is increasing evidence that highlight the importance of NK cell function during pulmonary tuberculosis (PTB), especially in the absence of optimal T-cell responses. Additionally, in the last years, it has been observed that NK cells mediate secondary responses against antigens to which they were previously exposed, an ability classically attributed to lymphocytes of the adaptive branch of immunity. This phenomenon, called "innate memory," could have important implications in the efforts to develop therapies and vaccines to improve the initial phases of immune reactions against different microorganisms, especially those to which there is not yet available vaccines to prevent infection, as is the case for tuberculosis. Therefore, the possibility of inducing memory-like NK cells ready to act prior to contact with Mtb or during the earliest stages of infection becomes quite interesting. However, our understanding of the mechanisms of innate memory remains incomplete. Here, we review recent literature about the mechanisms involved in the formation and maintenance of NK cell memory and the role of these cells in the immune response during tuberculosis. Finally, we discuss if the current evidence is sufficient to substantiate that NK cells exert more rapid and robust secondary responses after consecutive encounters with Mtb.
RESUMO
INTRODUCTION: Systemic sclerosis (SSc) shows variable clinical expression in different ethnic groups; vascular abnormalities are a prominent feature of this disease and its clinical expression may be influenced by genetic factors. PATIENTS AND METHODS: Herein, we describe 15 polymorphisms of the renin-angiotensin-aldosterone pathway in 170 Mexican admixed SSc patients (defined as patients with Mexican ancestry for at least 3 generations) and 199 healthy controls. We determined the presence of angiotensin II Type 1 receptor (AGTR1), angiotensin converting enzyme (ACE) and Endothelin 1 single nucleotide polymorphisms (SNPs) using 5' exonuclease TaqMan genotyping assays on a 7900HT real-time fast polymerase chain reaction (PCR) system. RESULTS: These polymorphisms had a similar distribution between SSc patients and controls, but we found that the AGTR1 G-680T (rs275652) (p = 0.02; OR 3.5; 95%CI 1.2-10.4) and AGTR1 A-119G (rs275653) (p = 0.008; OR 4.2; 95% CI 1.5-12.1) polymorphisms were associated with severe vascular involvement in our SSc patients. CONCLUSIONS: This is the first report of the association of these polymorphisms with vasculopathy in Mexican admixed SSc patients. Our findings suggested that the angiotensin II Type 1 receptor genotype may influence the clinical expression of vasculopathy in these patients. Functional analyses should follow.