EXPERIMENTAL REOVIRUS SEROTYPE-1 STRAIN LANG INFECTION OF THE LUNG - A MODEL FOR THE STUDY OF THE LUNG IN THE CONTEXT OF MUCOSAL IMMUNITY

A number of studies have examined the nature of the respiratory immune response to particular pathogens. Although many pathogens stimulate s pecific immunity in the lung, they frequently are not effective immuno gens at other mucosal sites. Because the gastrointestinal tract is a m ajor inductive site for mucosal immunity, a pathogen that is an effect ive respiratory and gut immunogen would allow studies of the interacti on 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 i nflammatory response occurs in the airspaces and interstitium of the l ung. As the infection progresses, the initially diffuse cellular infil trate becomes more focused around small bronchioles. Viral replication occurs predominantly during the first week of the infection, and infe ctious virions are eliminated during the second week. After the elimin ation of infectious virions, a secondary response consisting of the ap pearance of plasma cells adjacent to pulmonary arteries develops as th e primary infiltrate organizes into peribronchiolar follicles, resembl ing the human inflammatory lung condition termed follicular bronchioli tis. These two infiltration patterns were also observed by immunohisto chemical analysis of the the infected lung. Whereas CD4+ and CD8+ lymp hocytes and Mac-1+ cells were found to be more closely associated with the primary infiltration process, B220+ lymphocytes were observed adj acent to pulmonary arteries. These results establish respiratory reovi rus 1/L infection as a viable model for future investigations of the m ucosal immune response in the lung and its relationship to the common mucosal immune system.