Ookinete-induced midgut peroxidases detonate the time bomb in anopheline mosquitoes.

Previous analysis of the temporal-spatial relationship between ookinete migration and the cellular localization of genes mediating midgut immune defense responses suggested that, in order to survive, parasites must complete invasion before toxic chemicals ("a bomb") are generated by the invaded cell. Recent studies indicate that ookinete invasion induces tyrosine nitration as a two-step reaction, in which NOS induction is followed by a localized increase in peroxidase activity. Peroxidases utilize nitrite and hydrogen peroxide as substrates, and detonate the time bomb by generating reactive nitrogen intermediates, such as nitrogen dioxide, which mediate nitration. There is evidence that peroxidases also mediate antimicrobial responses to bacteria, fungi and parasites in a broad range of biological systems including humans and plants. Defense reactions that generate toxic chemicals are also potentially harmful to the host mounting the response and often results in apoptosis. The two-step nitration pathway is probably an ancient response, as it has also been described in vertebrate leukocytes and probably evolved as a mechanism to circumscribe the toxic products generated during defense responses involving protein nitration.