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.