Inhalation of Staphylococcus aureus enterotoxin A induces IFN-gamma and CD8 T cell-dependent airway and interstitial lung pathology in mice.
Staphylococcus aureus, a primary source of bacterial superantigen (SAg), is known to colonize the human respiratory tract and has been implicated in airway inflammation. Studies have documented a role for SAgs in respiratory disorders, such as nasal polyps, chronic obstructive pulmonary disease, chronic rhinosinusitis, and asthma. However, cellular and molecular mediators involved in SAg-mediated pulmonary disease have not been clearly identified. In this study, we investigated the effect of intranasal staphylococcal enterotoxin A (SEA) exposure on murine lung. The pathological features in the lung resulting from SEA exposure had characteristics of both obstructive and restrictive pulmonary disorders. There was also an increase in bronchoalveolar lavage protein concentration and cellularity following SEA challenge. Massive CD8(+)Vbeta3(+) T cell accumulation observed in the lung was dependent on CD4 T cell help, both for recruitment and for IFN-gamma synthesis. The primary source of IFN-gamma synthesis was CD8 T cells, and depletion of these cells abrogated disease. IFN-gamma deficiency also prevented SEA-mediated disease, and this was by enhancing early recruitment of neutrophils as detected in the bronchoalveolar lavage. Thus, IFN-gamma appeared to selectively aid the recruitment of T cells to the lungs while preventing the neutrophil accumulation. Therefore, our results show that IFN-gamma-producing CD8 T cells mediated pulmonary alveolitis and inflammation, which were dependent upon CD4 T cells for their recruitment to the lung.
Muralimohan
Guruprasaadh
G
Department of Immunology, University of Connecticut Health Center, Farmington, CT 06032, USA.
Rossi
Robert J
RJ
Guernsey
Linda A
LA
Thrall
Roger S
RS
Vella
Anthony T
AT
D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D004768:Enterotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D001239:Inhalation; D007371:Interferon-gamma / Q000096:biosynthesis*; D008168:Lung; D008171:Lung Diseases / Q000209:etiology*; D051379:Mice; D009504:Neutrophils
D004768:Enterotoxins; C026066:enterotoxin A, Staphylococcal; D007371:Interferon-gamma