Leishmania amazonensis fails to induce the release of reactive oxygen intermediates by CBA macrophages

Abstract

SummaryCBA 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 () and hydrogen peroxide (H2O2) by L. major- or L. amazonensis-infected CBA macrophages were measured. L. major induces macrophages to release levels of 3·5 times higher than in uninfected cells. This production is partially dependent on NADPH oxidase (NOX) type 2. The level of accumulated H2O2 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 production and H2O2 generation. Furthermore, these data reinforce the notion that L. amazonensis survive inside CBA macrophages by reducing ROS production during the phagocytic process.

Are Reactive Oxygen Species Always Detrimental to Pathogens?

“…How L. major uses FcR to enter the macrophages and still survive respiratory burst remains unknown. In fact, L. major parasites trigger intense ROS production upon macrophage infection, different from L. amazonensis, which proceeds through a relatively silent cell invasion (4). FcR most likely represent an entry portal to the macrophages at least in L. amazonensis or L. pifanoi, as FcR-deficient mice present smaller cutaneous lesions (142).…”

The Potential Role of Nrf2 Signaling in Leishmania Infection Outcomes

“…Infection with L. amazonensis usually induces very low oxidative stress (Almeida et al, 2012). L. amazonensis infection, compared to that of L. major, produces reduced levels of reactive oxygen intermediates, such as hydrogen peroxide, which is ∼20 times lower than that generated during L. major infection.…”

Cutaneous Manifestations of Human and Murine Leishmaniasis

“…Activation requires priming and activation signals, and TNF acts synergistically with IFNγ to induce NO and amastigote elimination by mouse macrophages ( Figure 4 ) [ 204 , 205 ]. In both human and murine macrophages, the respiratory burst is subverted by Leishmania virulence factors [ 206 , 207 ]. Phagocytosis of amastigotes induces even less superoxide formation compared with promastigotes [ 208 ].…”