Immunopathology of Leishmaniasis: Molecular and Cellular Mechanisms of Tissue Injury Provoked by Chronic Infection

Human infections caused by parasites represent a serious worldwide health issue, especially in underdeveloped countries. According to the World Health Organization, Leishmania ssp. is responsible for more than 70,000 deaths worldwide, mostly due to untreated visceral leishmaniasis (VL). Other species that cause non-deadly cutaneous infections are also relevant; they frequently leave disfiguring scars in infected patients, as seen in those with mucocutaneous leishmaniasis (MCL) or localised cutaneous leishmaniasis (LCL). Mechanisms of tissue injury provoked by chronic infections with different Leishmania ssp. correlate with immunological imbalances in the cellular and humoral immunological milieu. This parasite triggers host responses, including the activation of antibodies and complement, programmed cell death, uncontrolled cytokine synthesis, the production of reactive oxygen species and inflammation. If these responses are correctly balanced, they protect the infected host against chronic infection and relapse. However, when the right balance between these biological responses is disrupted, tissue damage occurs and frequently results in the death of those suffering from untreated VL or leaving disfiguring scars in MCL and LCL patients. Here, we review important mechanisms of tissue damage triggered by Leishmania species of human interest.