Induction, Propagation, and Activity of Host Nitric Oxide: Lessons from Leishmania Infection

The production of nitric oxide (NO) by the inducible NO synthase (iNOS) is a key defense mechanism against intracellular pathogens such as Leishmania. Numerous studies have investigated the antimicrobial properties of this small molecule in vitro but its precise mode of action during Leishmania infection in vivo is still unclear. In this review, we discuss how iNOS is induced in infected tissues and how NO acts to control the expansion of Leishmania parasites and limit tissue damage resulting from the infection. We highlight recently described mechanisms that result in widespread iNOS expression in infected tissues. We also discuss how the collective production and subsequent diffusion of NO generates an antimicrobial milieu that promotes parasite control at the tissue level.