Acquired resistance against a secondary infection with Listeria monocytogenes in mice is not dependent on reactive nitrogen intermediates

Abstract

During an infection, inflammatory mediators can induce the production of nitric oxide, a reactive nitrogen intermediate (RNI) which plays a role in antimicrobial activity against a wide variety of pathogens. In vitro experiments have shown that release of RNI by macrophages is mediated by tumor necrosis factor alpha (TNF). Since TNF is essential for acquired resistance during a secondary Listeria monocytogenes infection in mice, the aim of the present study was to determine whether RNI are also involved in the course of such an infection. Mice which had recovered from a sublethal primary infection with 0.1 50% lethal dose of (LD50) L. monocytogenes were infected intravenously with 10 LD50 of L. monocytogenes. During a primary infection, the number of bacteria in the liver and spleen, as well as the concentration of RNI in plasma, increased. During a secondary infection, the number of bacteria in the liver and spleen decreased whereas no significant increase in the concentration of RNI in plasma was observed. Neutralization of endogenously produced TNF and gamma interferon by subcutaneous injection of alginate-encapsulated monoclonal antibody-forming cells during a secondary infection resulted in an increase in the number of bacteria in the liver and spleen and an increase in the concentration of RNI in plasma. When the production of RNI was inhibited by treatment of mice with the competitive NO- synthase inhibitor N(ω)-nitro-L-arginine methyl ester hydrochloride (L- NAME) and an L-arginine-deficient diet during a secondary infection, the proliferation of L. monocytogenes in the liver and spleen was not affected whereas the concentration of RNI in plasma of these mice was significantly reduced. Our findings that inhibition of RNI formation during a secondary infection does not affect the proliferation of L. monocytogenes in the liver and spleen and that enhanced elimination of bacteria from these organs is nut accompanied by an increase in the concentration of RNI in plasma led to the conclusion that resistance against a secondary infection with L. monocytogenes is not dependent on RNI.