Protective and pathologic immune responses in human tegumentary leishmaniasis

Abstract

Studies in the recent years have advanced the knowledge of how host and parasite factors contribute to the pathogenesis of human tegumentary leishmaniasis. Polymorphism within populations of Leishmania from the same species has been documented; indicating that infection with different strains may lead to distinct clinical pictures and can also interfere in the response to treatment. Moreover, detection of parasite genetic tags for the precise identification of strains will improve diagnostics and therapy against leishmaniasis. On the host side, while a predominant Th1 type immune response is important to control parasite growth, it does not eradicate Leishmania and, in some cases, does not prevent parasite dissemination. Evidence has accumulated showing the participation of CD4(+) and CD8(+) T cells, as well as macrophages, in the pathology associated with L. braziliensis, L. guayanensis, and L. major infection. The discovery that a large percentage of individuals that are infected with Leishmania do not develop disease will help to understand how the host controls Leishmania infection. As these individuals have a weaker type 1 immune response than patients with cutaneous leishmaniasis, it is possible that control of parasite replication in these individuals is dependent, predominantly, on innate immunity, and studies addressing the ability of neutrophils, macrophages, and NK cells to kill Leishmania should be emphasized.

Keywords: Leishmania braziliensis; Leishmaniasis; immune response.

FIGURE 1

Parasite and host factors contribute to disease outcome in human L. braziliensis infection.Parasite polymorphisms are associated with clinical forms of the disease. The type of immune response developed by the host, determine whether parasite growth will be controlled or dissemination will occur. Detection of Leishmania in blood from SC individuals has not been achieved. Exaggerated pro-inflammatory immune response leads to tissue damage and ulcer development. Cells known to contribute to cytokines and CXCL9 production in L. braziliensis-infected patients are represented below the corresponding soluble factor. CL, cutaneous leishmaniasis; ML, mucosal leishmaniasis; DL, disseminated leishmaniasis; SC, sub-clinical.