Reactive Oxygen Species and Nitric Oxide in Cutaneous Leishmaniasis

Abstract

<jats:p>Cutaneous leishmaniasis affects millions of people around the world. Several species of<jats:italic>Leishmania</jats:italic>infect mouse strains, and murine models closely reproduce the cutaneous lesions caused by the parasite in humans. Mouse models have enabled studies on the pathogenesis and effector mechanisms of host resistance to infection. Here, we review the role of nitric oxide (NO), reactive oxygen species (ROS), and peroxynitrite (ONOO<jats:sup>−</jats:sup>) in the control of parasites by macrophages, which are both the host cells and the effector cells. We also discuss the role of neutrophil-derived oxygen and nitrogen reactive species during infection with<jats:italic>Leishmania</jats:italic>. We emphasize the role of these cells in the outcome of leishmaniasis early after infection, before the adaptive T<jats:sub>h</jats:sub>-cell immune response.</jats:p>

Leishmania donovani Prevents Oxidative Burst-mediated Apoptosis of Host Macrophages through Selective Induction of Suppressors of Cytokine Signaling (SOCS) Proteins

“…The Leishmania parasites are internalized by macrophages into phagolysosomes, where they display the remarkable ability to survive and replicate within this hostile environment. However, it is of interest to note that once internalized into macrophages, the parasite has to face severe oxidative stress inside the macrophages due to extensive production of reactive oxygen species (ROS) 2 (19). * This work was supported by Network Project Grant BSC 0206 and Supra Large quantities of ROS have been implicated as microbicidal agents in pathological situations and ultimately result in apoptosis of the macrophages harboring the pathogen, thereby resulting in parasite clearance (20).…”

A Defective TLR4 Signaling for IFN-β Expression Is Responsible for the Innately Lower Ability of BALB/c Macrophages to Produce NO in Response to LPS as Compared to C57BL/6

“…In contrast, cells from C57BL/6 mice (typical Th1 responders) produce a strong NO and citrulline response and seem to decrease their production of ornithine [3]. The differential ability of C57BL/6 and BALB/c macrophages to produce NO in vitro in response to IFN-γ and LPS or TNF-α had also been demonstrated by several groups, including ours [4]–[11]. C57BL/6 and BALB/c mice are broadly used as prototypes of resistance and susceptibility, respectively, to several infectious diseases.…”

Sodium nitroprusside has leishmanicidal activity independent of iNOS

“…Nitric oxide is well known to be a key effector in clearing Leishmania (21) , although the parasite is capable of suppressing nitric oxide production via several mechanisms (22) (23) . Thus, drugs that release nitric oxide, including sodium nitroprusside (24) , may enhance leishmanicidal activity in macrophages.…”