β-Glucan-Induced Trained Immunity Protects against Leishmania braziliensis Infection: a Crucial Role for IL-32

Abstract

Summary: American tegumentary leishmaniasis is a vector-borne parasitic disease caused by Leishmania protozoans. Innate immune cells undergo long-term functional reprogramming in response to infection or Bacillus Calmette-Guérin (BCG) vaccination via a process called trained immunity, conferring non-specific protection from secondary infections. Here, we demonstrate that monocytes trained with the fungal cell wall component β-glucan confer enhanced protection against infections caused by Leishmania braziliensis through the enhanced production of proinflammatory cytokines. Mechanistically, this augmented immunological response is dependent on increased expression of interleukin 32 (IL-32). Studies performed using a humanized IL-32 transgenic mouse highlight the clinical implications of these findings in vivo. This study represents a definitive characterization of the role of IL-32γ in the trained phenotype induced by β-glucan or BCG, the results of which improve our understanding of the molecular mechanisms governing trained immunity and Leishmania infection control. : dos Santos et al. describe that trained immunity induced by β-glucan confers protection against L. braziliensis infections. Infection control is associated with IL-32 and IL-1 induction. Genetic variation in the IL-32 gene enhances induction of trained immunity leading to proinflammatory gene transcription in bone marrow hematopoietic stem and progenitor cells. Keywords: Leishmania braziliensis, trained immunity, β-glucan, BCG, IL-32, proinflammatory cytokines, IL-32 transgenic mouse