The Role of Nitric Oxide and Reactive Oxygen Species in the Killing of <i>Leishmania braziliensis</i> by Monocytes from Patients with Cutaneous Leishmaniasis

<div><p>Human cutaneous leishmaniasis (CL) caused by <i>Leishmania braziliensis</i>, presents an exaggerated Th1 response that is associated with ulcer development. Macrophages are the primary cells infected by <i>Leishmania</i> parasites and both reactive oxygen species (ROS) and nitric oxide (NO) are important in the control of <i>Leishmania</i> by these cells. The mechanism involved in the killing of <i>L</i>. <i>braziliensis</i> is not well established. In this study, we evaluate the role of ROS and NO in the control of <i>L</i>. <i>braziliensis</i> infection by monocytes from CL patients. After <i>in vitro</i> infection with <i>L</i>. <i>braziliensis</i>, the oxidative burst by monocytes from CL patients was higher when compared to monocytes from healthy subjects (HS). Inhibition of the ROS pathway caused a significant decrease in the oxidative burst in <i>L</i>. <i>braziliensis</i> infected monocytes from both groups. In addition, we evaluated the intracellular expression of ROS and NO in <i>L</i>. <i>braziliensis</i>-infected monocytes. Monocytes from CL patients presented high expression of ROS after infection with <i>L</i>. <i>braziliensis</i>. The expression of NO was higher in monocytes from CL patients as compared to expression in monocytes from HS. A strong positive correlation between NO production and lesion size of CL patients was observed. The inhibition of ROS production in leishmania-infected monocytes from CL patients allowed the growth of viable promastigotes in culture supernatants. Thus, we demonstrate that while production of ROS is involved in <i>L</i>. <i>braziliensis</i> killing, NO alone is not sufficient to control infection and may contribute to the tissue damage observed in human CL.</p>