Infection of mice with Mycobacterium bovis-BCG induces both Th1 and Th2 immune responses in the absence of interferon-gamma signalling.
A murine pulmonary infection model using Mycobacterium bovis-BCG was used to study the development of Th1 and Th2 type responses in mice lacking a functional IFN-gamma receptor (IFN-gamma R-/-). Strikingly, the IFN-gamma R-/- mice maintained the Th1 response and developed a profound M. bovis-BCG, specific Th2 type immune response characterized by IL-5-producing CD4+ T cells, eosinophil infiltration of granulomas, and significantly elevated serum IgE levels. The increase in IL-5 production and eosinophil recruitment into the lung could be detected within the first 1-2 weeks of infection, indicating that the Th2 response was not due to greatly enhanced bacterial numbers observed later in infection. These results clearly indicate that IFN-gamma acts during M. bovis-BCG infection to suppress the development of Th2 immune responses. Furthermore, they demonstrate that IFN-gamma is not a necessary cofactor in the development of Th1 type cells secreting IFN-gamma. In conclusion, these data demonstrate that IFN-gamma plays a major role in suppressing a potentially disease-promoting Th2 immune response during mycobacterial infections.
Zentrum für Infektionsforschung, Universität Würzburg, Röntgenring 11, 97070 Würzburg, Germany. zinf036@rzroe.uni-wuerzburg.de
K J
KJ
Erb
J
J
Kirman
B
B
Delahunt
H
H
Moll
G
G
Le Gros
D000818:Animals; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000209:etiology / Q000473:pathology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology* / Q000302:isolation & purification; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000276:immunology / Q000382:microbiology; D000096743:Interferon gamma Receptor
D007073:Immunoglobulin E; D007074:Immunoglobulin G; D007371:Interferon-gamma; D008222:Lymphokines; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor