The role of nitric oxide in the innate resistance to microfilariae of Litomosoides sigmodontis in mice

Nitric oxide (NO) has been shown to be an important effector mechanism in t he defence against various pathogens, including filariae. The production of NO, as well as H2O2, is induced by the Th1 cytokine IFN-gamma. Therefore, the microfilariae (mf) of filarial nematodes, which are known to elicit the release of IFN-gamma, may be a target of NO release. In this study, we fou nd that Inf of the filarial species Litomosoides sigmodontis were resistant to the attack of H2O2, but vulnerable to NO exposure in vitro by a chemica l NO donor, as well as activated macrophages. Adult worms were considerably less affected by exposure to NO. In-vivo production of NO following inject ion of mf in this and previous studies, suggested a central role in the def ence to filariae. However, neither pharmaceutical inhibition of nitric oxid e synthesis, nov generic knockout of the gene for inducible nitric oxide sy nthase (iNOS), abrogated resistance to circulating mf in mice, interestingl y, however, iNOS-KO mice showed higher interleukin (IL)-2 responses and low er IL-10 production, compared to their wild-type counterparts. in conclusio n, despite its effectiveness in vitro and the observed production of NO by ex vivo cells following infection, nitric oxide seems not to be an importan t factor in elimination of wf of L. sigmodontis in vivo. However, it may ha ve a regulatory role in the immune response.