Immunological Aspects of Leishmaniasis: A Review on the Latest Developments

Abstract

Leishmaniasis is a vector-borne disease of ancient origin caused by protozoan parasites of the genus Leishmania and transmitted by female phlebotomine sand flies, with an estimated 1.7 to 3 million new cases and approximately 20,000 deaths each year, concentrated in poor rural and semirural communities. Unlike many other vector-borne infections, Leishmania does not establish a self-limiting infection in the vertebrate host: it escapes the innate response and persists within a tissue-resident macrophage reservoir, producing a clinical spectrum that extends from asymptomatic carriage to cutaneous, mucosal and visceral disease. This review synthesises current understanding of the immunological basis of that spectrum. It follows the response from the moment of inoculation sand fly saliva, complement deposition, the early neutrophil influx and phagocyte uptake through dendritic-cell priming to the polarisation of CD4+ T-helper subsets, and examines how the Th1/Th2 balance, together with Th17 and regulatory T cells, separates control of infection from progressive disease. Macrophage activation states, the tissue-specific immune microenvironments of skin and mucosa, and species- and strain-specific evasion strategies are considered in turn, alongside the genetic and epigenetic determinants that modulate susceptibility. The review then examines the translation of this knowledge into practice through immune-based diagnostic biomarkers, vaccine strategies directed at immune pathways, and immunomodulatory therapies given alongside conventional drugs. Persisting gaps are identified, in particular the absence of a licensed vaccine for visceral leishmaniasis and the lack of a gold-standard laboratory method for diagnosis.