Reconciling protective and pathogenic roles of the NLRP3 inflammasome in leishmaniasis

Leishmaniasis is a global health problem that affects more than 2 billion people worldwide. Recent advances in research have demonstrated critical roles for cytoplasmic sensors and inflammasomes during Leishmania spp. infection and pathogenesis. Specifically, several studies have focused on the role of nod-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome and inflammasome-associated cytokines IL-1β and IL-18 in leishmaniasis. Despite these studies, our understanding of the priming and activation events that lead to NLRP3 inflammasome activation during Leishmania spp. infection is limited. Furthermore, whether NLRP3 plays a protective or pathogenic role during Leishmania spp. infection is far from resolved, with some studies showing a protective role and others showing a pathogenic role. In this review, we performed a critical review of the literature to provide a current update on priming and activating signals required for NLRP3 inflammasome activation during Leishmania spp. infection. Finally, we provide a thorough review of the literature to reconcile differences in the observed protective vs pathogenic roles of the NLRP3 inflammasome during Leishmania spp. infection.