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15-fold compared with control (Figure 1). Chemokines, which coordinate the recruitment of leucocytes involved in homeostasis and in innate and adaptive immune responses, play a crucial role in the regulation of immunity against Leishmania. In addition, CCL3 and CCL20 have been shown to display antiparasitic activity against the promastigote form of the Leishmania mexicana parasite by acting directly on plasma membranes on Leishmania parasites, causing their lysis. Evidence of an increase in phagocytosis and NO-mediated destruction of Leishmania by chemokines (including CCL3 and CCL4) was reported a decade ago. Moreover, we show here that IL-23A levels are induced by GSNO. Murray et al. showed that IL-23 displayed an antileishmanial effect, especially during late-stage parasitic infection. Thus, GSNO may be implicated in a cellular signalling pathway leading to macrophage activation and exhibiting immunostimulatory effects. Our results indicate that GSNO not only exhibits microcidal activity but also acts as a macrophage activator. This activation was possible with the involvement of at least three chemokines (CCL4, CCL3 and CCL20) and one cytokine (IL23A). All of them are known to have antiparasitic activity, and thus could be effective against Leishmania infection. In conclusion, our results may be relevant to investigators working on GSNO antiparasitic activity in vitro and in vivo.

the journal of antimicrobial chemotherapy/journal of antimicrobial chemotherapy

S-nitrosoglutathione (GSNO) is cytotoxic to intracellular amastigotes and promotes healing of topically treated Leishmania major or Leishmania braziliensis skin lesions--authors' response