gammadelta T cells regulate the early inflammatory response to bordetella pertussis infection in the murine respiratory tract.
The role of gammadelta T cells in the regulation of pulmonary inflammation following Bordetella pertussis infection was investigated. Using a well-characterized murine aerosol challenge model, inflammatory events in mice with targeted disruption of the T-cell receptor delta-chain gene (gammadelta TCR-/- mice) were compared with those in wild-type animals. Early following challenge with B. pertussis, gammadelta TCR-/- mice exhibited greater pulmonary inflammation, as measured by intra-alveolar albumin leakage and lesion histomorphometry, yet had lower contemporaneous bacterial lung loads. The larger numbers of neutrophils and macrophages and the greater concentration of the neutrophil marker myeloperoxidase in bronchoalveolar lavage fluid from gammadelta TCR-/- mice at this time suggested that differences in lung injury were mediated through increased leukocyte trafficking into infected alveoli. Furthermore, flow cytometric analysis found the pattern of recruitment of natural killer (NK) and NK receptor+ T cells into airspaces differed between the two mouse types over the same time period. Taken together, these findings suggest a regulatory influence for gammadelta T cells over the early pulmonary inflammatory response to bacterial infection. The absence of gammadelta T cells also influenced the subsequent adaptive immune response to specific bacterial components, as evidenced by a shift from a Th1 to a Th2 type response against the B. pertussis virulence factor filamentous hemagglutinin in gammadelta TCR-/- mice. The findings are relevant to the study of conditions such as neonatal B. pertussis infection and acute respiratory distress syndrome where gammadelta T cell dysfunction has been implicated in the inflammatory process.
Zachariadis
O
O
Department of Veterinary Pathology, Faculty of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Cassidy
J P
JP
Brady
J
J
Mahon
B P
BP
D000818:Animals; D001885:Bordetella Infections / Q000503:physiopathology*; D001886:Bordetella pertussis; D015964:Gene Expression Regulation, Bacterial; D007249:Inflammation / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000502:physiology*; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D016692:Receptors, Antigen, T-Cell, gamma-delta