Chauhan, YogeshNikita, RajkumariMadaan, PriyankaJain, Manju2024-01-162024-08-132024-01-162024-08-132023-01-319789811982255978981198224810.1007/978-981-19-8225-5_11https://doi.org/10.1007/978-981-19-8225-5_11http://10.2.3.109/handle/32116/2915Leishmaniasis is a disease complex with clinical manifestations ranging from systemic visceral leishmaniasis (VL) to cutaneous leishmaniasis (CL) with skinrestricted lesions to mucocutaneous leishmaniasis (MCL) that extends to mucous membranes. These classical disease outcomes are understood as an outcome of the infecting parasite species/subspecies along with the immune correlates that define host immune status. Further each of the visceral, cutaneous and/or mucocutaneous disease forms exhibits heterogenous gradation of parasite load, extent of parasite dissemination and collateral host immunopathological damage that may result in asymptomatic, mild, moderate or severe disease phenotype. A complex network of crosstalk between immune cells, viz. neutrophils, macrophages and heterogenous T cells, with varied effector immune molecules defines the disease protective versus progressive response. Unlike a clear Th1 versus Th2 immune response in VL and CL murine models, the immune correlates in classical VL and CL human subjects exhibit a mixed response with considerable heterogeneity. A net balance of the inflammatory versus antiinflammatory immune response induced by the complement of antigen pool presented by discrete parasite species along with the immune regulation mediated by T regulatory cells drives the immunopathological outcome. Such immune heterogeneity extends to a newer disease phenomenon of atypical leishmaniasis wherein the parasite species classically known to cause VL is reported to cause cutaneous disease and vice versa. The biology of such atypical leishmaniasis cases is beginning to be explored in terms of the host immune changes apart from the differences in the parasite determinants. The chapter seeks to highlight the host immune heterogeneity that is associated with different disease outcomes in a classical setting along with atypical clinical manifestations. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.en-USAtypical leishmaniasisClassical leishmaniasisImmune heterogeneityLeishmaniasisBook chapter