Immunodeficient mice are remarkably resistant to Listeria monocytogenes (LM) infection. We examined the role that nitric oxide (NO) plays in the CB- 17/lcr SCID (SCID) response to LM. SCID spleen cells produced large quantities of NO (as measured by nitrite formation) when incubated in the presence of heat-killed LM. NO production was dependent on the release of IFN-γ by the SCID NK cells. When tested directly, macrophages produced large quantities of nitrite in response to LM, but only in the presence of IFN-γ. The production of NO induced by LM was not affected by neutralizing antibodies to TNF or IL-1. The production of NO was inhibited by addition of either of two inhibitors of NO synthase, N(G)-monomethyl arginine, or aminoguanidine. In a different situation, NK cells that were stimulated by TNF and Listeria products to release IFN-γ did not produce NO. Macrophages cultured with IFN-γ killed live LM. This increased killing of LM was significantly inhibited by amino-guanidine. In vivo, administration of aminoguanidine resulted in a marked increase in the mortality and spleen bacterial loads of LM-infected SCID or immunocompetent control mice. We conclude that NO is a critical effector molecule of T cell-independent natural resistence to LM as studied in the SCID mouse, and that the NO- mediated response is essential for both SCID and immunocompetent host to survive after LM infection.
|Number of pages||8|
|Journal||Journal of Immunology|
|State||Published - 1993|