RESUMEN
Viruses which infect mucosal surfaces commonly infect these particular anatomical sites based on both the virion structure and the interaction of the virus with a particular microenvironment. We infected a human lung epithelial cell line, a human gut epithelial cell line, and a human lung fibroblast cell line with reovirus 1/L to explore how this natural isolate of both the lung and the gut may interact with mucosal surfaces. While reovirus infection of the gut and lung epithelial cell lines was lytic, a chronic infection was established in the human lung fibroblast cell line. All three cell lines also produced interleukin-8 (IL-8) after infection with reovirus 1/L, and IL-8 production was not dependent upon viral replication. A prolonged production of IL-8 was observed in the chronically infected lung fibroblast cell line, suggesting that this mucosal population may be involved in the generation of inflammatory responses after the resolution of the initial lytic infection of the epithelium. These studies provide an in vitro model system for analyzing the interaction of reovirus 1/L with resident mucosal cell populations.
Asunto(s)
Interleucina-8/genética , Orthoreovirus/inmunología , Línea Celular , Células Epiteliales , Fibroblastos , Regulación de la Expresión Génica , Humanos , Inmunidad Mucosa , Inflamación/genética , Inflamación/inmunología , Interleucina-8/biosíntesis , Membrana Mucosa/inmunología , Membrana Mucosa/virología , Orthoreovirus/clasificación , Orthoreovirus/patogenicidad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Infecciones por Reoviridae/genética , Infecciones por Reoviridae/inmunología , SerotipificaciónRESUMEN
Bronchiolitis obliterans organizing pneumonia (BOOP) is a term that was first applied in 1985 to describe a long-observed but unclassified pattern of acute lung injury. BOOP lesions are characterized by fibrous extensions into the alveolar spaces in association with a peribronchiolar organizing pneumonia. Since 1985, an increasing number of reports of BOOP have appeared in the clinical literature, and it is now accepted that BOOP is a significant pulmonary syndrome. Although BOOP can be associated with a number of documented pulmonary insults, many cases are not associated with known causes and are thus classified as idiopathic. The lack of an appropriate small animal model that closely mimics the generation of BOOP lesions has been an impediment to basic studies of the pathogenic mechanisms responsible for the generation of BOOP in humans. In this report, we describe an animal model for BOOP in which CBA/J mice infected with reovirus serotype 1/strain Lang develop BOOP lesions. These lesions closely resemble those seen in humans and occur in a well defined temporal sequence that proceeds from initial peribronchiolar inflammatory lesions to characteristic, fibrotic cellular BOOP lesions over a 3-week time course.
Asunto(s)
Neumonía en Organización Criptogénica/virología , Modelos Animales de Enfermedad , Orthoreovirus , Infecciones por Reoviridae/patología , Animales , Neumonía en Organización Criptogénica/patología , Relación Dosis-Respuesta Inmunológica , Femenino , Fibrosis/patología , Fibrosis/virología , Inmunohistoquímica , Ratones , Ratones Endogámicos CBA , Microscopía Electrónica , Infecciones por Reoviridae/virología , Factores de Tiempo , Proteínas Virales/análisisRESUMEN
Respiratory virus infections are a serious health challenge. While models exist to study immune mechanisms of the respiratory tract, they have not allowed analysis of the interaction of the lower respiratory tract with other components of the mucosal immune system. This study demonstrates that reovirus 1/Lang, an effective gut mucosal immunogen, also provides a useful model of respiratory mucosal infection. Intra-nasal infection of Balb/c mice resulted in severe viral bronchopneumonia. Major components of the cellular inflammatory response in the lung interstitium and alveolar spaces were CD8 lymphocytes. Lung lymphocyte populations exhibited lysis of reovirus-infected, but not uninfected target cells after in vitro culture. The GCT antigen, a germinal center B-cell and CD8 T-cell marker, was present on 21-60% of the inflammatory lymphocytes. A novel population of GCT-expressing CD4+ lymphocytes unique to reovirus-stimulated lung alveolar and interstitial lymphocyte populations was identified.
Asunto(s)
Pulmón/inmunología , Activación de Linfocitos , Infecciones por Reoviridae/inmunología , Reoviridae/inmunología , Subgrupos de Linfocitos T/inmunología , Enfermedad Aguda , Animales , Antígenos de Diferenciación de Linfocitos T/análisis , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/virología , Pruebas Inmunológicas de Citotoxicidad , Femenino , Inmunofenotipificación , Ganglios Linfáticos/inmunología , Mediastino , Ratones , Ratones Endogámicos BALB C , Membrana Mucosa/inmunología , Mucosa Nasal/inmunología , Mucosa Nasal/virología , Reoviridae/crecimiento & desarrollo , Infecciones por Reoviridae/etiología , Infecciones por Reoviridae/patología , Subgrupos de Linfocitos T/clasificación , Subgrupos de Linfocitos T/virología , Replicación Viral/inmunologíaRESUMEN
A number of studies have examined the nature of the respiratory immune response to particular pathogens. Although many pathogens stimulate specific immunity in the lung, they frequently are not effective immunogens at other mucosal sites. Because the gastrointestinal tract is a major inductive site for mucosal immunity, a pathogen that is an effective respiratory and gut immunogen would allow studies of the interaction of the lung with gut mucosal immune system. Reovirus, a respiratory isolate that previously has been shown to be an effective gut mucosal immunogen, provides a potential model of the relationship of the lung to the gut mucosal immune system. In this report, we demonstrate that intranasal application of reovirus serotype 1/strain Lang (1/L) to CD-1 mice elicits an acute lymphocytic inflammatory infiltration of the lung and hyperplasia of the lung-associated lymph nodes. The initial inflammatory response occurs in the airspaces and interstitium of the lung. As the infection progresses, the initially diffuse cellular infiltrate becomes more focused around small bronchioles. Viral replication occurs predominantly during the first week of the infection, and infectious virions are eliminated during the second week. After the elimination of infectious virions, a secondary response consisting of the appearance of plasma cells adjacent to pulmonary arteries develops as the primary infiltrate organizes into peribronchiolar follicles, resembling the human inflammatory lung condition termed follicular bronchiolitis. These two infiltration patterns were also observed by immunohistochemical analysis of the the infected lung. Whereas CD4+ and CD8+ lymphocytes and Mac-1+ cells were found to be more closely associated with the primary infiltration process, B220+ lymphocytes were observed adjacent to pulmonary arteries. These results establish respiratory reovirus 1/L infection as a viable model for future investigations of the mucosal immune response in the lung and its relationship to the common mucosal immune system.