Innate immunity against Leishmania infections

Abstract

Leishmaniasis is a major health problem that affects more than 300 million people throughout the world. The morbidity associated with the disease causes serious economic burden in Leishmania endemic regions. Despite the morbidity and economic burden associated with Leishmaniasis, this disease rarely gets noticed and is still categorized under neglected tropical diseases. The lack of research combined with the ability of Leishmania to evade immune recognition has rendered our efforts to design therapeutic treatments or vaccines challenging. Herein, we review the literature on Leishmania from innate immune perspective and discuss potential problems as well as solutions and future directions that could aid in identifying novel therapeutic targets to eliminate this parasite.

Keywords: Leishmania; NLR; TLR; complement.

Figure 1. Innate immune responses against Leishmania infections

(A) Upon entry into the mammalian hosts, Leishmania parasites first come in contact with the complement system. Once the complement pathway is activated, C3b facilitates C5b-C9 membrane attack complex (MAC) on the Leishmania surface and lyses the parasite. Conversely, Leishmania virulence factor LPG inhibits MAC complex formation on the surface, while GP63 inactivates C3b (iC3b) and inhibits MAC complex. Opsonization of Leishmania by C3b and iC3b facilitates its uptake by CD11b and FcγR receptor on neutrophils and macrophages. (B) TLR2 and TLR4 on macrophage recognize Leishmania outside, whereas TLR3 and TLR9 recognizes Leishmania in the vacuole. Activation of TLRs activates the NFκB and MAP kinase signaling through MyD88 which is important for Leishmania clearance. In the cytoplasm, NLRP3 inflammasome senses Leishmania to produce IL-1β and IL-18, which can have diverse cellular functions depending on the genetic background of the host.