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.