Roles of cytokines in host defense to bacterial infection in mice

Background. Antigen-specific CD4(+) helper T (Th) cell responses can be div ided into Th1, and Th2, based on cytokine production. Differentiation of Th 1 cells, which can produce IL-2, IFN-gamma. and lymphotoxin, is driven by I L-12 and IFN-gamma, while differentiation of Th2 cells, which produce IL-4, IL-5, IL-10, and IL-13, depends on IL-4. We studied the production and rol es of Th1- and Th2-derived cytokines in bacterial infections such as a facu ltative intracellular-growing Listeria monocytogenes (L. monocytogenes) and an extracellular-growing Staphylococcus aureus (S. aureus) in mice. Methods. Female C57BL/6, C57BL/6-IFN-gamma(-/-), and ddY mice were used. Mi ce were infected intravenously (iv) with L. monocytogenes or S, aureus. Mon oclonal antibodies (mAbs) against IFN-gamma, IL-4, IL-IO, and IL-12 p40 wer e injected iv into mice 2 h before infection. Cytokines in the bloodstream, spleen extracts, and spleen cell culture supernatants were estimated by EL ISAs or RT-PCR. Results: Th1-type responses were observed in vivo and in vitro in L. monocy togenes infected mice. IFN-gamma(-/-) mice were highly susceptible to L. mo nocytogenes infection, compared with IFN-gamma(+/+) mice. Administration of anti-IFN-gamma mAb or anti-IL-l2 mAb also attenuated antilisterial resista nce and induced Th2-type responses in immunocompetent mice. On the other ha nd, Th2-type responses were observed in vitro in S, aureus infected mice. I FN-gamma(-/-) mice were more resistant to S. aureus infection, compared wit h IFN-gamma(+/+) mice. Administration of anti-IL-4 mAb or anti-IL-10 mAb at tenuated the host defense. Conclusions. These results suggest that Th1-type cytokines are responsible for host defense to a facultative intracellular-growing L. monocytogenes. I n contrast, host defense to an extracellular-growing S. aureus is shown to be dependent on Th2-type cytokines.