RESUMEN
Data were extracted from the case records of UK patients admitted with laboratory-confirmed influenza A(H1N1)pdm09. White and non-White patients were characterized by age, sex, socioeconomic status, pandemic wave and indicators of pre-morbid health status. Logistic regression examined differences by ethnicity in patient characteristics, care pathway and clinical outcomes; multivariable models controlled for potential confounders. Whites (n = 630) and non-Whites (n = 510) differed by age, socioeconomic status, pandemic wave of admission, pregnancy, recorded obesity, previous and current smoking, and presence of chronic obstructive pulmonary disease. After adjustment for a priori confounders non-Whites were less likely to have received pre-admission antibiotics [adjusted odds ratio (aOR) 0·43, 95% confidence interval (CI) 0·28-0·68, P < 0·001) but more likely to receive antiviral drugs as in-patients (aOR 1·53, 95% CI 1·08-2·18, P = 0·018). However, there were no significant differences by ethnicity in delayed admission, severity at presentation for admission, or likelihood of severe outcome.
Asunto(s)
Etnicidad/estadística & datos numéricos , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/terapia , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , Vías Clínicas/estadística & datos numéricos , Femenino , Disparidades en Atención de Salud/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Grupos Raciales/estadística & datos numéricos , Factores Sexuales , Factores Socioeconómicos , Reino Unido/epidemiología , Adulto JovenRESUMEN
A role for interleukin-21 (IL-21) has recently been found in several diseases, but contribution to mucosal defences has not been described. In BALB/c mice infected with respiratory syncytial virus (RSV), IL-21 depletion had little effect in primary infection. However, depletion of mice during priming with recombinant vaccinia expressing RSV G protein (which primes RSV-specific T helper type 2 cells and causes lung eosinophilia during RSV infection) further exacerbated pathology during RSV challenge, with reduced viral clearance and impaired virus-specific serum antibody responses. This enhancement was accompanied by lymphocyte, neutrophil, and antigen-presenting cell recruitment to the lungs, with increased bronchoalveolar lavage interferon-γ and IL-17 levels. Adoptive transfer of splenic CD4 T cells from depleted mice into naive recipients replicated these effects, indicating that IL-21 mediates its effects via CD4 T cells. Endogenous IL-21, therefore, has potent and specific effects on mucosal antiviral responses, assisting viral clearance, regulating pulmonary T- and B-cell responses, and inhibiting IL-17 production.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Interleucinas/metabolismo , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/metabolismo , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones por Virus Sincitial Respiratorio/metabolismo , Virus Sincitiales Respiratorios/inmunología , Traslado Adoptivo , Animales , Formación de Anticuerpos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Citocinas/biosíntesis , Femenino , Interferón gamma/metabolismo , Interleucina-17/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/virología , Ratones , Infecciones por Virus Sincitial Respiratorio/terapiaRESUMEN
The inflammatory response to lung infections must be tightly regulated, enabling pathogen elimination while maintaining crucial gas exchange. Using recently described "depletion of regulatory T cell" (DEREG) mice, we found that selective depletion of regulatory T cells (Tregs) during acute respiratory syncytial virus (RSV) infection enhanced viral clearance but increased weight loss, local cytokine and chemokine release, and T-cell activation and cellular influx into the lungs. Conversely, inflammation was decreased when Treg numbers and activity were boosted using interleukin-2 immune complexes. Unexpectedly, lung (but not draining lymph node) Tregs from RSV-infected mice expressed granzyme B (GzmB), and bone marrow chimeric mice with selective loss of GzmB in the Treg compartment displayed markedly enhanced cellular infiltration into the lung after infection. A crucial role for GzmB-expressing Tregs has not hitherto been described in the lung or during acute infections, but may explain the inability of children with perforin/GzmB defects to regulate immune responses to infection. The effects of RSV infection in mice with defective immune regulation closely parallel the observed effects of RSV in children with bronchiolitis, suggesting that the pathogenesis of bronchiolitis may involve an inability to regulate virus-induced inflammation.
Asunto(s)
Bronquiolitis Viral/inmunología , Granzimas/metabolismo , Neumonía Viral/inmunología , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitiales Respiratorios/inmunología , Linfocitos T Reguladores/metabolismo , Enfermedad Aguda , Animales , Anticuerpos/metabolismo , Complejo Antígeno-Anticuerpo/administración & dosificación , Bronquiolitis Viral/etiología , Bronquiolitis Viral/prevención & control , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Niño , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Granzimas/genética , Granzimas/inmunología , Humanos , Interleucina-2/inmunología , Interleucina-2/metabolismo , Pulmón/inmunología , Pulmón/patología , Pulmón/virología , Depleción Linfocítica , Ratones , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/terapia , Virus Sincitiales Respiratorios/patogenicidad , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patología , Linfocitos T Reguladores/virología , Carga Viral/efectos de los fármacos , Carga Viral/inmunologíaRESUMEN
BACKGROUND: During the first wave of pandemic H1N1 influenza in 2009, most cases outside North America occurred in the UK. The clinical characteristics of UK patients hospitalised with pandemic H1N1 infection and risk factors for severe outcome are described. METHODS: A case note-based investigation was performed of patients admitted with confirmed pandemic H1N1 infection. RESULTS: From 27 April to 30 September 2009, 631 cases from 55 hospitals were investigated. 13% were admitted to a high dependency or intensive care unit and 5% died; 36% were aged <16 years and 5% were aged > or = 65 years. Non-white and pregnant patients were over-represented. 45% of patients had at least one underlying condition, mainly asthma, and 13% received antiviral drugs before admission. Of 349 with documented chest x-rays on admission, 29% had evidence of pneumonia, but bacterial co-infection was uncommon. Multivariate analyses showed that physician-recorded obesity on admission and pulmonary conditions other than asthma or chronic obstructive pulmonary disease (COPD) were associated with a severe outcome, as were radiologically-confirmed pneumonia and a raised C-reactive protein (CRP) level (> or = 100 mg/l). 59% of all in-hospital deaths occurred in previously healthy people. CONCLUSIONS: Pandemic H1N1 infection causes disease requiring hospitalisation of previously fit individuals as well as those with underlying conditions. An abnormal chest x-ray or a raised CRP level, especially in patients who are recorded as obese or who have pulmonary conditions other than asthma or COPD, indicate a potentially serious outcome. These findings support the use of pandemic vaccine in pregnant women, children <5 years of age and those with chronic lung disease.
Asunto(s)
Hospitalización/estadística & datos numéricos , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/diagnóstico , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Niño , Preescolar , Cuidados Críticos/estadística & datos numéricos , Brotes de Enfermedades , Inglaterra/epidemiología , Femenino , Humanos , Lactante , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Neumonía Viral/epidemiología , Neumonía Viral/virología , Pronóstico , Factores de Riesgo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza , Gripe Humana/epidemiología , Gripe Humana/inmunología , Pandemias , Adyuvantes Inmunológicos , Costos de la Atención en Salud , Humanos , Inmunidad , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Gripe Humana/prevención & control , Gripe Humana/transmisión , Vacunación Masiva/tendencias , Reino UnidoRESUMEN
Although known as respiratory pathogens, severe acute respiratory syndrome (SARS) and its sister coronaviruses frequently cause enteric symptoms. In addition, other classically non-enteric viruses (such as HIV and influenza) may also have enteric effects that are crucial in their pathogeneses. These effects can be due to direct infection of the gut mucosa, but can also be because of decreased antibacterial defenses, increased mucosal permeability, bacterial translocation, and systemic leak of endotoxin.
Asunto(s)
Infecciones por Coronavirus/virología , Tracto Gastrointestinal/virología , Pulmón/virología , Ganglios Linfáticos Agregados/virología , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/virología , Coronavirus/metabolismo , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/microbiología , Enteritis/complicaciones , Enteritis/microbiología , Enteritis/virología , Tracto Gastrointestinal/microbiología , Infecciones por VIH/complicaciones , Infecciones por VIH/microbiología , Infecciones por VIH/virología , VIH-1/metabolismo , Humanos , Gripe Humana/complicaciones , Gripe Humana/microbiología , Gripe Humana/virología , Pulmón/microbiología , Ganglios Linfáticos Agregados/microbiología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/metabolismo , Síndrome Respiratorio Agudo Grave/complicaciones , Síndrome Respiratorio Agudo Grave/microbiología , Síndrome Respiratorio Agudo Grave/virologíaRESUMEN
BACKGROUND: The mechanisms underlying exacerbation of asthma induced by respiratory syncytial virus (RSV) infection have been extensively studied in human and animal models. However, most of these studies focused on acute inflammation and little is known of its long-term consequences on remodelling of the airway tissue. OBJECTIVE: The aim of the study was to use a murine model of prolonged allergen-induced airway inflammation to investigate the effect of RSV infection on allergic airway inflammation and tissue remodelling. METHODS: We subjected mice to RSV infection before or during the chronic phase of airway challenges with OVA and compared parameters of airway inflammation and remodelling at the end-point of the prolonged allergen-induced airway inflammation protocol. RESULTS: RSV infection did not affect the severity of airway inflammation in any of the groups studied. However, RSV infection provoked airway remodelling in non-sensitized, allergen-challenged mice that did not otherwise develop any of the features of allergic airways disease. Increased collagen synthesis in the lung and thickening of the bronchial basal membrane was observed in non-sensitized allergen-challenged mice only after prior RSV infection. In addition, fibroblast growth factor (FGF)-2 but not TGF-beta(1) was increased in this group following RSV infection. CONCLUSION: Our data show for the first time that RSV infection can prime the lung of mice that are not previously systemically sensitized, to develop airway remodelling in response to allergen upon sole exposure via the airways. Moreover, our results implicate RSV-induced FGF-2 in the remodelling process in vivo.
Asunto(s)
Asma/patología , Pulmón/patología , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitiales Respiratorios , Compuestos de Alumbre/administración & dosificación , Análisis de Varianza , Animales , Asma/inmunología , Asma/virología , Líquido del Lavado Bronquioalveolar/inmunología , Colágeno/metabolismo , Citocinas/metabolismo , Matriz Extracelular/metabolismo , Femenino , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Inmunohistoquímica , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/virología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/administración & dosificación , Ovalbúmina/inmunología , Infecciones por Virus Sincitial Respiratorio/metabolismo , Infecciones por Virus Sincitial Respiratorio/patología , Estadísticas no Paramétricas , Factor de Crecimiento Transformador beta/metabolismoAsunto(s)
Asma/virología , Bronquiolitis Viral/complicaciones , Receptores de Antígenos de Linfocitos T gamma-delta/análisis , Infecciones por Virus Sincitial Respiratorio/complicaciones , Subgrupos de Linfocitos T/inmunología , Asma/inmunología , Bronquiolitis Viral/inmunología , Humanos , Infecciones por Virus Sincitial Respiratorio/inmunología , Factores de RiesgoRESUMEN
Infants who recover from respiratory syncytial virus (RSV)-induced bronchiolitis are at high risk of developing asthma and recurrent wheezing. It is not known whether severe RSV infection itself causes persistent effects or is a marker of a "wheezy" predisposition. To determine the long-term immunological correlates of infantile bronchiolitis, interleukin (IL)-4 and interferon (IFN)-gamma responses to a panel of antigens were studied in a well-characterised cohort of 7-8-yr-old children with a history of severe RSV bronchiolitis in infancy. Peripheral blood lymphocytes from 37 children who were hospitalised with RSV bronchiolitis in infancy and from 69 age-, sex- and location-matched controls were stimulated in vitro with RSV, house-dust mite, birch and cat antigens. Cellular proliferation, and enzyme-linked immunoSPOT IFN-gamma and IL-4 production were measured. IL-4 producing T-cells responding to RSV and cat antigens were significantly more frequent in exbronchiolitics. Other responses (including the IFN-gamma response to RSV) were equally strong in exbronchiolitics and controls. Respiratory syncytial virus infection primes memory T-cells that make interferon-gamma, but virus and aeroallergen-specific and interleukin-4 producing T-cells are also frequently primed in bronchiolitics. Respiratory syncytial virus bronchiolitis in infancy may increase the risk of allergic sensitisation by providing a local interleukin-4-rich environment, in which airborne allergens are first encountered.
Asunto(s)
Asma/etiología , Asma/inmunología , Bronquiolitis Viral/complicaciones , Bronquiolitis Viral/inmunología , Interferón gamma/inmunología , Interleucina-4/inmunología , Ruidos Respiratorios/etiología , Ruidos Respiratorios/inmunología , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitiales Respiratorios/patogenicidad , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Técnicas In Vitro , Lactante , Interferón gamma/análisis , Interleucina-4/análisis , Masculino , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
BACKGROUND: Asthma, atopy and some forms of respiratory syncytial virus (RSV) disease are thought to be caused by T cells making IL-4 (Th2 cells). However, not all patients with similar patterns of clinical disease have the same underlying pathogenesis and the ability to detect immunopathogenic T cells by examination of the peripheral blood remains in doubt. With the prospect of specific immunotherapy for diseases caused by T cell subsets, it is important to determine whether peripheral blood mononuclear cell (PBMC) reactivity can be used to establish the presence of immunopathogenic responses and therefore to predict therapeutic effects. OBJECTIVE: To detect IL-4 and IFN-gamma production as markers of Th1 and Th2 responses in the peripheral blood of atopic and asthmatic adults. METHODS: PBMC from 22 adult asthmatics (18 of whom were atopic) and 21 non-asthmatic volunteers (ten of whom were atopic) were stimulated with cat, birch and house dust mite allergens, human rhinovirus, RSV and recombinant chimaeric F/G protein from RSV in vitro. ELISPOT assays were used to enumerate cells producing IL-4 and IFN-gamma. RESULTS: Asthmatics had a sixfold increase in frequencies of IL-4-producing cells to cat and birch allergen (median values: 37 vs. 7 per million PBMC, P < 0.01 and 20 vs. 3 per million PBMC, P < 0.04, respectively) compared to non-asthmatics. By contrast, non-asthmatic atopics showed no specific increase in antigen-specific IL-4 responses and there was no evident correlation between skin prick test reactivity and ELISPOT results. Atopics had significantly more IFN-gamma-producing cells specific for FG than nonatopics. while IFN-gamma and IL-4 responses to other antigens were not significantly different. CONCLUSION: Enhanced IL-4 responses to non-viral aeroallergens are seen in adults with asthma, while enhanced IFN-gamma responses to viral antigen FG were see in atopics. In practical terms, ELISPOT assays for specific cytokines may provide a method that could be used to monitor antigen-specific T cell responses in peripheral blood.
Asunto(s)
Alérgenos/inmunología , Asma/inmunología , Interleucina-4/biosíntesis , Células Th2/inmunología , Adulto , Anciano , Animales , Antígenos Dermatofagoides/inmunología , Antígenos de Plantas , Antígenos Virales/inmunología , Proteínas de Artrópodos , Gatos , Cisteína Endopeptidasas , Femenino , Glicoproteínas/inmunología , Humanos , Hipersensibilidad Inmediata/inmunología , Interferón gamma/biosíntesis , Masculino , Persona de Mediana Edad , Proteínas de Plantas/inmunología , Polen/inmunología , Virus Sincitiales Respiratorios/inmunología , Pruebas Cutáneas , Células TH1/inmunologíaRESUMEN
Inducing a strong immune response is an essential aim of vaccination. Although immune responses to virus infections are usually protective, they can also be harmful. The best-documented examples of an immune response increasing disease severity are with dengue, measles and respiratory syncytial virus infections. In the 1960s, administration of formalin-inactivated, tissue culture grown RSV (FI-RSV) was found to induce strong ELISA binding but poor virus-neutralising antibody. Infants given this 'lot 100' vaccine appeared to exhibit an increased rate of RSV infection during subsequent natural RSV outbreaks. Although it has not been possible to exactly delineate the cause of disease enhancement in man, animal models strongly suggest that it was due to strong (and perhaps unbalanced) T cell priming rather than infection-enhancing or sensitising antibody. In animal models, enhanced disease can result from over-exuberant T cell priming which recruits an abundant inflammatory infiltrate in the lung (the nature of which depends on the patterns of cytokines and chemokines produced). Formalin-treated RSV vaccination has been linked specifically to the induction of Th2 cells, which make IL-4 and IL-5 and induce a strong pulmonary eosinophilic response. The vaccine dosing regime and the interval between vaccination and challenge can be critical to the induction of protection or pathology. Defining the correlates of protection and disease enhancement in man is critical to the rational development of effective and protective vaccines against RSV.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio/etiología , Vacunas contra Virus Sincitial Respiratorio/efectos adversos , Animales , Anticuerpos Antivirales/inmunología , Humanos , Inmunidad Celular , Inmunoglobulina G/inmunología , Modelos AnimalesRESUMEN
TNF antagonists are effective treatments for rheumatoid arthritis and Crohn's disease, and have been tried with variable success in other diseases caused by immune damage. To test the hypothesis that viral lung diseases caused by respiratory syncytial virus or influenza virus are partly due to overproduction of TNF, we used anti-TNF antibody to treat mice with lung disease caused by these viruses. TNF depletion reduced pulmonary recruitment of inflammatory cells, cytokine production by T cells and the severity of illness without preventing virus clearance. These broad beneficial effects suggest that TNF antagonists might be tested as treatments of human viral lung diseases.
Asunto(s)
Bronquiolitis Viral/inmunología , Infecciones por Virus Sincitial Respiratorio/inmunología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Anticuerpos/farmacología , Anticuerpos Antivirales/biosíntesis , Bronquiolitis Viral/patología , Bronquiolitis Viral/virología , Citocinas/biosíntesis , Femenino , Pulmón/inmunología , Pulmón/patología , Pulmón/virología , Recuento de Linfocitos , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/patología , Eosinofilia Pulmonar/inmunología , Infecciones por Virus Sincitial Respiratorio/patología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitiales Respiratorios/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/fisiología , Pérdida de PesoRESUMEN
T cells secreting interleukin (IL)-4 and IL-5 (T helper cell type 2 [Th2] cells) play a detrimental role in a variety of diseases, but specific methods of regulating their activity remain elusive. T1/ST2 is a surface ligand of the IL-1 receptor family, expressed on Th2- but not on interferon (IFN)-gamma-producing Th1 cells. Prior exposure of BALB/c mice to the attachment (G) or fusion (F) protein of respiratory syncytial virus (RSV) increases illness severity during intranasal RSV challenge, due to Th2-driven lung eosinophilia and exuberant Th1-driven pulmonary infiltration, respectively. We used these polar models of viral illness to study the recruitment of T1/ST2 cells to the lung and to test the effects of anti-T1/ST2 treatment in vivo. T1/ST2 was present on a subset of CD4(+) cells from mice with eosinophilic lung disease. Monoclonal anti-T1/ST2 treatment reduced lung inflammation and the severity of illness in mice with Th2 (but not Th1) immunopathology. These results show that inhibition of T1/ST2 has a specific effect on virally induced Th2 responses and suggests that therapy targeted at this receptor might be of value in treating Th2-driven illness.
Asunto(s)
Proteínas de la Membrana , Proteínas/inmunología , Receptores de Interleucina-1/inmunología , Infecciones por Virus Sincitial Respiratorio/inmunología , Linfocitos T Colaboradores-Inductores , Animales , Eosinofilia/inmunología , Eosinofilia/terapia , Femenino , Proteína 1 Similar al Receptor de Interleucina-1 , Ratones , Ratones Endogámicos BALB C , Receptores de Interleucina , Infecciones por Virus Sincitial Respiratorio/terapia , Células TH1 , Células Th2Asunto(s)
Asma/virología , Bronquiolitis Viral/inmunología , Bronquiolitis Viral/virología , Infecciones por Virus Sincitial Respiratorio/inmunología , Animales , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antivirales/uso terapéutico , Asma/inmunología , Asma/prevención & control , Bronquiolitis Viral/complicaciones , Modelos Animales de Enfermedad , Humanos , Inmunización , Lactante , Ratones , Palivizumab , Eosinofilia Pulmonar/inmunología , Eosinofilia Pulmonar/virología , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/genéticaAsunto(s)
Asma/inmunología , Infecciones Bacterianas/inmunología , Virosis/inmunología , Niño , Preescolar , Humanos , LactanteRESUMEN
Bronchiolitis caused by respiratory syncytial virus (RSV) infection is a major cause of hospitalization in children under 1 year of age. RSV causes common colds in older children and adults, but can cause serious disease in immunodeficient patients and the elderly. Development of effective vaccines and treatments for RSV infection is therefore a priority. Because bronchiolitis and vaccine-augmented disease are thought to be caused by exuberant T cell activation, attention has focused on the use of immunomodulators that affect T cell responses. In mice, IL-12 treatment down-regulates type 2 cytokine responses to the attachment protein G of RSV, reducing lung eosinophilia but further enhancing illness. We now show that CD8(+) T cells are responsible for enhanced weight loss, whereas IL-12-activated NK cells express high levels of IFN-gamma and inhibit lung eosinophilia without causing illness. Moreover, unlike immunocompetent mice, virus is detected in the mediastinal lymph nodes after elimination of both CD8(+) T cells and NK cells. These studies show that innate immune responses to viral infections direct the pattern of subsequent specific immunity and are critical to the development of nonpathogenic antiviral effects. We speculate that IL-12 treatment might be beneficial and safe in T cell-deficient patients with RSV pneumonitis.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Proteína HN/fisiología , Interleucina-12/fisiología , Células Asesinas Naturales/inmunología , Linfopenia/inmunología , Eosinofilia Pulmonar/inmunología , Eosinofilia Pulmonar/prevención & control , Virus Sincitiales Respiratorios/fisiología , Proteínas Virales/fisiología , Animales , Antivirales/farmacología , Linfocitos T CD8-positivos/patología , Movimiento Celular/inmunología , Citocinas/biosíntesis , Inyecciones Intraperitoneales , Interferón gamma/farmacología , Interferón gamma/fisiología , Interleucina-12/administración & dosificación , Activación de Linfocitos/inmunología , Linfopenia/virología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Eosinofilia Pulmonar/fisiopatología , Eosinofilia Pulmonar/virología , Índice de Severidad de la Enfermedad , Subgrupos de Linfocitos T/inmunología , Proteínas del Envoltorio ViralRESUMEN
The effect of infection history is ignored in most animal models of infectious disease. The attachment protein of respiratory syncytial virus (RSV) induces T helper cell type 2-driven pulmonary eosinophilia in mice similar to that seen in the failed infant vaccinations in the 1960s. We show that previous influenza virus infection of mice: (a) protects against weight loss, illness, and lung eosinophilia; (b) attenuates recruitment of inflammatory cells; and (c) reduces cytokine secretion caused by RSV attachment protein without affecting RSV clearance. This protective effect can be transferred via influenza-immune splenocytes to naive mice and is long lived. Previous immunity to lung infection clearly plays an important and underestimated role in subsequent vaccination and infection. The data have important implications for the timing of vaccinations in certain patient groups, and may contribute to variability in disease susceptibility observed in humans.