Abstract
BackgroundReactive oxygen species (ROS) protect the host against a large number of pathogenic microorganisms. ROS have different effects on parasites of the genus Leishmania: some parasites are susceptible to their action, while others seem to be resistant. The role of ROS in L. amazonensis infection in vivo has not been addressed to date.MethodsIn this study, C57BL/6 wild-type mice (WT) and mice genetically deficient in ROS production by phagocytes (gp91phox−/−) were infected with metacyclic promastigotes of L. amazonensis to address the effect of ROS in parasite control. Inflammatory cytokines, parasite loads and myeloperoxidase (MPO) activity were evaluated. In parallel, in vitro infection of peritoneal macrophages was assessed to determine parasite killing, cytokine, NO and ROS production.ResultsIn vitro results show induction of ROS production by infected peritoneal macrophages, but no effect in parasite killing. Also, ROS do not seem to be important to parasite killing in vivo, but they control lesion sizes at early stages of infection. IFN-γ, TNF-α and IL-10 production did not differ among mouse strains. Myeloperoxidase assay showed augmented neutrophils influx 6 h and 72 h post - infection in gp91phox−/− mice, indicating a larger inflammatory response in gp91phox−/− even at early time points. At later time points, neutrophil numbers in lesions correlated with lesion size: larger lesions in gp91phox−/− at earlier times of infection corresponded to larger neutrophil infiltrates, while larger lesions in WT mice at the later points of infection also displayed larger numbers of neutrophils.ConclusionROS do not seem to be important in L. amazonensis killing, but they regulate the inflammatory response probably by controlling neutrophils numbers in lesions.
Highlights
Reactive oxygen species (ROS) protect the host against a large number of pathogenic microorganisms
Once it was determined that L. amazonensis metacyclic promastigotes could stimulate ROS production by macrophages, we proceeded to investigate if ROS would have an effect on the course of infection with this parasite
Gp91phox−/− mice develop larger lesions after infection with L. amazonensis To address the importance of ROS during L. amazonensis infection, we infected mice deficient in the gp91phox subunit of NOX2
Summary
Reactive oxygen species (ROS) protect the host against a large number of pathogenic microorganisms. ROS have different effects on parasites of the genus Leishmania: some parasites are susceptible to their action, while others seem to be resistant. Leishmaniasis are a spectrum of diseases caused by parasites of the genus Leishmania. This disease is endemic in 88 countries and affects two million people every year. The diseases may present themselves as cutaneous, mucocutaneous or visceral forms, depending on which species is involved in the infection [1]. In the well-established model of infection of mice with L. major, resistance to several parasite strains is mediated. Macrophages are the main host cell for Leishmania spp. When infected with these parasites, macrophages sustain Leishmania spp. growth.
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