Reactive oxygen species and nitric oxide in cutaneous leishmaniasis

Abstract

Cutaneous leishmaniasis affects millions of people around the world. Several species of Leishmania 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(-)) 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 Leishmania. We emphasize the role of these cells in the outcome of leishmaniasis early after infection, before the adaptive T(h)-cell immune response.

Figure 1

Infection with L. major induces more TNF than infection with L. amazonensis. (a) TNF production by inflammatory macrophages from C57BL/10, mice infected in vitro with L. major or L. amazonensis. (b) Production of TNF ex vivo by lymph node cells from C3H/HeN, C57BL/10 and BALB/c mice infected with L. major or L. amazonensis, 2 days after infection. A biological assay that does not distinguish between TNF-α or TNF-β was used in these experiments. These are representative experiments of more than five performed experiments (L. Q. Vieira and P. Scott, unpublished).

Figure 2

Course of infection with L. amazonensis in wild-type C57BL/6 and Nox2 knockout mice (a) and parasite quantitation using a limiting dilution analysis (b). *indicates statistical difference by Student's t test, P < 0.05 (E. H. Roma and J. P. Macedo, unpublished).