The role of IL-32 in Bacillus Calmette-Guerin (BCG)-induced trained immunity in infections caused by different Leishmania spp.

Background: Cells of the innate immune system undergo long-term functional reprogramming in response to Bacillus Calmette-Gue acute accent rin (BCG) exposure via a process called trained immunity, conferring nonspecific protection to unrelated infections. Here, we investigate whether BCG-induced trained immunity is able to protect against infections caused by different Leishmania spp., protozoa that cause cutaneous and mucosal or visceral lesions. Methods: We used training models of human monocytes with BCG and subsequent infection by L. braziliensis, L. amazonensis and L. infantum, and the vaccination of wild-type and transgenic mice for IL-32 gamma before in vivo challenge with parasites. Results: We demonstrated that monocytes trained with BCG presented enhanced ability to kill L. braziliensis, L. amazonensis and L. infantum through increased production of reactive oxygen species. Interleukin (IL)-32 appears to play an essential role in the development of trained immunity. Indeed, BCG exposure induced IL-32 production in human primary monocytes, both mRNA and protein. We have used a human IL-32 gamma transgenic mouse model (IL-32 gamma Tg) to study the effect of BCG vaccination in different Leishmania infection models. BCG vaccination decreased lesion size and parasite load in infections caused by L. braziliensis and reduced the spread of L. amazonensis to other organs in both infected wild-type (WT) and IL-32 gamma Tg mice. In addition, BCG reduced the parasite load in the spleen, liver and bone marrow of both WT and IL-32 gamma Tg mice infected with L. infantum. BCG vaccination increased inflammatory infiltrate in infected tissues caused by different Leishmania spp. In all infections, the presence of IL-32 gamma was not mandatory, but it increased the protective and inflammatory effects of BCG-induced training. Conclusions: BCG's ability to train innate immune cells, providing protection against leishmaniasis, as well as the participation of IL-32 gamma in this process, pave the way for new treatment strategies for this neglected infectious disease.

Automated summary

BCG-induced trained immunity enhances the killing ability of monocytes against different Leishmania spp. through increased production of reactive oxygen species. IL-32 plays a crucial role in the development of trained immunity, and BCG vaccination shows protective effects against Leishmania infections.