The role of IL-32 in Bacillus Calmette-Guérin (BCG)-induced trained immunity in infections caused by different Leishmania spp.
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Data
2021
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Gra-bretanha
Resumo
Background: Cells of the innate immune system undergo long-term functional reprogramming in response to
Bacillus Calmette-Gu´erin (BCG) exposure via a process called trained immunity, conferring nonspecific protec tion 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-32γ 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-32γ transgenic
mouse model (IL-32γTg) 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-32γTg mice. In addition, BCG reduced
the parasite load in the spleen, liver and bone marrow of both WT and IL-32γTg 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-32γ 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-32γ in this process, pave the way for new treatment strategies for this neglected infectious
disease.
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Leishmania, Human, IL-32γTg mouse, BCG IL-32
Citação
SILVA, Muriel Vilela Teodoro et al. The role of IL-32 in Bacillus Calmette-Guérin (BCG)-induced trained immunity in infections caused by different Leishmania spp. Microbial Pathogenesis, London, v. 158, e105088, 2021. DOI: 10.1016/j.micpath.2021.105088. Disponível em: https://www.sciencedirect.com/science/article/pii/S0882401021003600?via%3Dihub. Acesso em: 21 jan. 2025.