The Enigma of CD1d-iNKT Axis in Leishmaniases: Current Insights Into Immune Regulation

Leishmaniases caused by Leishmania parasites may be fatal if proper treatment is lacking. These protozoan parasites employ several strategies to control the host immune system. Among these, manipulation of the antigen presentation pathway is crucial for survival in the host. In addition to protein antigens produced by Leishmania sp. parasite-derived lipid or glycolipid antigens are known which are potentially important at the interface of host-parasite interactions. CD1d is a cell surface-expressed receptor that presents both endogenous and exogenous lipids and glycolipids to the TCR of invariant NKT cells. The CD1d-iNKT axis is important during the initial stages of infection by several species of Leishmania, although it may not be required for resolution of the infection at a later stage in mice. Owing to the limited number of published reports, heterogeneity in response is evident in both mice and human. Organ-specific, host species-specific and parasite species-specific responses make the concept even more complex. In this review, we comprehensively summarise the role of the CD1d-iNKT axis in the regulation of Leishmania infection. A deeper understanding of the mechanistic role of the CD1d-iNKT axis during Leishmania infection in human may provide a foundation for the rational design of targeted immunotherapeutic interventions in the future.