The multifaceted role of cAMP signalling in Leishmania pathogenesis and host immune modulation.

Cyclic adenosine monophosphate (cAMP) is a pivotal second messenger involved in regulating numerous cellular processes, including apoptosis, kinase activation, immune responses, and cell cycle progression. In the context of Leishmania infection, emerging evidence highlights how different Leishmania species exploit host and parasite-derived cAMP signalling pathways to modulate host cell functions and promote their survival. This review consolidates current understanding of parasite-mediated modulation of host defence mechanisms through cAMP signalling, thereby emphasising its crucial role in establishing and maintaining a permissive intracellular environment. Furthermore, it elaborates on how cAMP-driven pathways regulate the expression of antioxidant enzymes, inflammatory cytokines and apoptosis, thereby orchestrating immune suppression and facilitating long-term parasite persistence within the host. Moreover, Leishmania further harnesses its endogenous cAMP signalling pathway to drive its differentiation and replication within the host. Understanding these molecular tactics has not only enriched basic science but also opened new avenues for therapeutic interventions. This review underscores the centrality of cAMP signalling in Leishmania pathogenesis and highlights the therapeutic promise of targeting these pathways to develop more effective treatments against leishmaniasis.