Leishmaniasis and IFN-γ dependent chemokines.

Abstract

Leishmaniasis is a disease caused by Leishmania and spread by the bite of certain types of sandflies. Leishmaniasis affects as many as 12 million people worldwide, with 2 million new cases each year. Leishmania infection, and Leishmaniasis, following occupational exposure has been also reported. Three forms of Leishmaniasis are known: a- Cutaneous Leishmaniasis (CL); b-Mucocutaneous Leishmaniasis; c- Visceral Leishmaniasis (VL). The visceral form of Leishmaniasis has an estimated incidence of 500,000 new cases. Cytokines and chemokines primarily orchestrate leukocyte recruitment to the areas of leishmania infection, and they are critical mediators of immune and inflammatory responses, in particular of the induction of Interferon (IFN)-γ and IFN-γ dependent chemokines. Skin biopsies from patients with CL showed higher expression of interferon-γ-induced protein (IP)-10, in recent lesions than in late lesions. Following L. braziliensis infection, enhanced expression of IP-10 and its receptor, chemokine C-X-C receptor (CXCR) 3, was predominantly detected in CD14(+) monocyte; this may contribute to disease severity by increasing cellular recruitment. It has been shown that IP-10 renders protection against VL, and it is associated with a strong host-protective T helper cell (Th)1 immune response. High clinical scores were positively correlated with IP-10 expression. Furthermore IP-10 is critical for rendering a protective cellular immunity during soluble leishmanial antigen (SLA) pulsed-CpG-ODN stimulated dendritic cells (SLA-CpG-DCs) vaccination that confers protection against L. donovani infection. Further studies are needed to evaluate IP-10 in Leishmaniosis, and to evaluate it as a potential therapeutic target.