Leishmania Viannia guyanensis, LRV1 virus and extracellular vesicles: a dangerous trio influencing the faith of immune response during muco-cutaneous leishmaniasis

•New world Leishmania species L.V. guyanensis and L.V. braziliensis harbor LRV1 virus that can exacerbate the disease.•LLRV1 can exit from Leishmania enveloped within exosomes enhancing virus transmission and impact on leishmaniasis progression.•In macrophages LRV1 trigger TLR3 activation leading to TRIF-mediated Type I Interferon production and autophagy induction.•LRV1-induced autophagy inhibits NLRP3 inflammasome activation, influencing parasite replication and disease exacerbation. Parasites of Leishmania genus have developed various strategies to overcome host immune response favoring its infection and development toward leishmaniasis. With an array of virulence factors, those parasites modify host macrophage signaling and functions. Depending of the species involved, visceral or cutaneous leishmaniasis will develop. Several years ago, Leishmania Viannia guyanensis that is naturally infected with the endosymbiotic virus Leishmania RNA Virus 1 was found to cause a particularly aggressive form of South-American mucocutaneous leishmaniasis. This virus, when co-transmitted with the parasite was shown to strongly modulate RNA sensors and NLRP3 inflammasome network that could explain in part the exacerbated skin pathology caused by this particular parasite. In this review, we will be discussing how this endosymbiotic virus-infected Leishmania in conjunction with Leishmania exosomes partner together to manipulate host immune response in their favor.