Production of nitric oxide (NO) is not essential for protection against acute Toxoplasma gondii infection in IRF-1-/- mice
Khan, I.A.; Matsuura, T.; Fonseka, S.; Kasper, L.H.
Journal of Immunology 156(2): 636-643
1996
ISSN/ISBN: 0022-1767 PMID: 8543815 Document Number: 468342
Mice, with a targeted disruption of the interferon (IFN) regulatory factor-1 gene (IRF-1-/-), were used to investigate the importance of nitric oxide (NO) in the host immune response against Toxoplasma gondii. IRF-1-/- mice were more susceptible to acute Toxoplasma infection, and treatment with either exogenous IFN- gamma or in vivo neutralization of endogenous IFN- gamma had little effect on their susceptibility to infection. However, administration of exogenous IL-12 was able to prolong survival even when IFN- gamma was depleted. An in vivo depletion study suggested that the mechanism of this protective response is mediated in part by CD4+ T cells. The administration of IL-12 could not overcome the inhibition of the lymphoproliferative response in T. gondii-infected mice and treatment with N-monomethyl-L-arginine (-NMMA), a nitric oxide synthase (iNOS) antagonist in vitro was unable to reverse the immunosuppression. In response to Toxoplasma infection, splenocytes from IRF-1-/- mice exhibited increased production of IL-10 as well as a 30-fold increase in its message expression. These studies indicate that NO may not be essential for host immunity to the parasite, and moreover that IL-12 appears to induce an IFN- gamma -independent mechanism of protection against this opportunistic pathogen.