IFN-gamma knockout mice show Th2-associated delayed-type hypersensitivity and the inflammatory cells fail to localize and control chlamydial infection

Delayed-type hypersensitivity (DTH) has been demonstrated to be a Th1 type immune response which is important in the host defense against infection wi th intracellular bacteria, including Chlamydia. In the present study, we su rprisingly observed that C. trachomatis mouse pneumonitis (MoPn)-infected I FN-gamma gene knockout (KO) mice mounted strong DTH responses following foo pad challenge with inactivated organisms. The DTH responses in IFN-gamma KO mice were associated with Th2 cytokine production and partially blocked by anti-IL-4 monoclonal antibodies. In addition, the inflammatory cells in IF N-gamma KO mice failed to target the cellular sites of chlamydial inclusion s in infected tissues and failed to clear the infection. The data, in conju nction with previous studies, suggest that different types (Th1 and Th2 ass ociated) of DTH responses may function differently in host defense against chlamydial infection and that the functional differences in DTH responses m ay account for the dual role that DTH is speculated to play in chlamydial p rotective immunity and immunopathology. Moreover, the data suggest that the IFN-gamma KO mouse is a useful model system for studying chlamydial pathog enesis.