Impact of reactive oxygen species (ROS) on the control of parasite loads and inflammation in Leishmania amazonensis infection (original) (raw)
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Reactive Oxygen Species and Nitric Oxide in Cutaneous Leishmaniasis
Journal of Parasitology Research, 2012
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. the outcome of the disease [1]. Cutaneous leishmaniasis is caused by several species of the genus Leishmania, including L. major, L. tropica, L. aethiopica, L. mexicana, L. braziliensis, L. guyanensis, L. panamensis, L. peruviana, and L. amazonensis. The Leishmania genus is divided in two subgenera, Leishmania and Viannia. In the subgenus Leishmania, L. amazonensis, L. mexicana (complex L. mexicana), and L. major (complex L. major) are by far the most studied species that cause cutaneous leishmaniasis. The subgenus Viannia comprises two important species that cause cutaneous leishmaniasis, L. guyanensis (complex L. guyanensis) and L. braziliensis (complex L. braziliensis) .
The Dangerous Liaisons in the Oxidative Stress Response to Leishmania Infection
Pathogens
Leishmania parasites preferentially invade macrophages, the professional phagocytic cells, at the site of infection. Macrophages play conflicting roles in Leishmania infection either by the destruction of internalized parasites or by providing a safe shelter for parasite replication. In response to invading pathogens, however, macrophages induce an oxidative burst as a mechanism of defense to promote pathogen removal and contribute to signaling pathways involving inflammation and the immune response. Thus, oxidative stress plays a dual role in infection whereby free radicals protect against invading pathogens but can also cause inflammation resulting in tissue damage. The induced oxidative stress in parasitic infections triggers the activation in the host of the antioxidant response to counteract the damaging oxidative burst. Consequently, macrophages are crucial for disease progression or control. The ultimate outcome depends on dangerous liaisons between the infecting Leishmania s...
Parasite Immunology, 2012
CBA mouse macrophages effectively control Leishmania major infection, yet are permissive to Leishmania amazonensis. It has been established that some Leishmania species are destroyed by reactive oxygen species (ROS). However, other species of Leishmania exhibit resistance to ROS or even down-modulate ROS production. We hypothesized that L. amazonensis-infected macrophages reduce ROS production soon after parasite-cell interaction. Employing a highly sensitive analysis technique based on chemiluminescence, the production of superoxide (O ÁÀ 2) and hydrogen peroxide (H 2 O 2) by L. majoror L. amazonensis-infected CBA macrophages were measured. L. major induces macrophages to release levels of O ÁÀ 2 3AE5 times higher than in uninfected cells. This O ÁÀ 2 production is partially dependent on NADPH oxidase (NOX) type 2. The level of accumulated H 2 O 2 is 20 times higher in L. major-than in L. amazonensis-infected cells. Furthermore, macrophages stimulated with L. amazonensis release amounts of ROS similar to uninfected cells. These findings support previous studies showing that CBA macrophages are effective in controlling L. major infection by a mechanism dependent on both O ÁÀ 2 production and H 2 O 2 generation. Furthermore, these data reinforce the notion that L. amazonensis survive inside CBA macrophages by reducing ROS production during the phagocytic process.