NO contributes to proliferative suppression in a murine model of filariasis.
Infection of BALB/c mice with microfilariae (mf) of Brugia pahangi leads to the suppression of antigen (Ag)-specific proliferative responses in the spleen. The proliferative defect is dependent on inducible nitric oxide synthase (iNOS) activity, since inhibition of iNOS with either L-N-monomethyl arginine (L-NMMA) or aminoguanidine reversed defective proliferation. Splenocytes from mf-infected animals produce high levels of gamma interferon (IFN-gamma) upon in vitro restimulation with Ag, and experiments in IFN-gamma receptor-deficient (IFN-gamma R(-/-)) mice demonstrated that signaling via the IFN-gamma R is essential in the induction of NO production and subsequent proliferative suppression. Restimulation of splenocytes from mf-infected animals with an extract of Acanthocheilonema viteae, a related filarial worm which lacks endosymbiotic bacteria, also resulted in NO production and proliferative suppression, demonstrating that lipopolysaccharide of bacterial origin is not essential to the induction of iNOS activity. These results extend previous observations that infection with different life cycle stages of Brugia leads to the development of differentially polarized immune responses and demonstrate one method by which these differences may exert their effects on the proliferative potential of cells from infected animals.
O'Connor
R A
RA
Department of Veterinary Parasitology, University of Glasgow, Glasgow G61 1QH, United Kingdom.
Jenson
J S
JS
Devaney
E
E
D000818:Animals; D000941:Antigens / Q000276:immunology; D017209:Apoptosis; D005368:Filariasis / Q000276:immunology*; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D017471:Receptors, Interferon / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology; D000096743:Interferon gamma Receptor
D000941:Antigens; D007371:Interferon-gamma; D007376:Interleukin-2; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D017471:Receptors, Interferon; D019323:omega-N-Methylarginine; D000096743:Interferon gamma Receptor; C496317:Nos2 protein, mouse