title: Interferon-gamma and nitric oxide production are not required for the immune-mediated clearance of Brugia malayi microfilariae in mice.
abstract: Previous research has shown that Brugia malayi microfilariae (Mf) primarily induce type 1 cytokine production, and that in-vitro nitric oxide (NO) can mediate Mf killing. This study addresses the role of interferon (IFN)-gamma-mediated immune responses in the clearance of Mf from fast-clearing (CBA/Ca) and slow-clearing (C57Bl/6) mouse strains. Analysis of spleen cell cytokine production at early timepoints p.i. showed that Mf-induced IFN-gamma and nitrite (NO-) levels were significantly greater in CBA/Ca mice than C57Bl/6 mice. However, in-vivo neutralization of IFN-gamma or inhibition of NO- production in CBA/Ca mice did not alter Mf survival kinetics. Similarly, the rate of Mf clearance in both C57Bl/6 mice lacking the IFN-gamma gene and (C57Bl/6 x 129) mice deficient in the receptor for IFN-gamma was similar to that of wild-type animals. Furthermore, the dramatic abrogation of NO- production in IFN-gammaR-/- mice suggests that Mf clearance in slow-clearing mouse strains is also independent of NO- production. Thus, in both rapid-clearing and slow-clearing mouse strains, IFN-gamma-mediated mechanisms are not a requirement for Mf clearance from the bloodstream.
authors.affiliation: School of Biological Sciences, 3.239 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Gray
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Lawrence
mesh_terms: D000818:Animals; D017178:Brugia malayi / Q000254:growth & development / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005368:Filariasis / Q000276:immunology* / Q000469:parasitology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology*; D008018:Life Cycle Stages; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D008842:Microfilariae / Q000302:isolation & purification; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D017471:Receptors, Interferon / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology; D000096743:Interferon gamma Receptor
chemical_list: D004791:Enzyme Inhibitors; D007371:Interferon-gamma; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017471:Receptors, Interferon; D019323:omega-N-Methylarginine; D000096743:Interferon gamma Receptor