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Cell Rep. 2019 Sep 3;28(10):2659-2672.e6. doi: 10.1016/j.celrep.2019.08.004.

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

Author information

1
Radboud Institute for Molecular Sciences (RILMS), Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
2
Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
3
Myeloid Cell Biology, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany.
4
Radboud Institute for Molecular Sciences (RILMS), Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark; Odense Patient Data Explorative Network, University of Southern Denmark and Odense University Hospital, Odense, Denmark.
5
Radboud Institute for Molecular Sciences (RILMS), Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
6
Radboud Institute for Molecular Sciences (RILMS), Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
7
Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
8
Myeloid Cell Biology, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany; Single Cell Genomics and Epigenomics Unit at the German Center for Neurodegenerative Diseases and the University of Bonn, 53175 Bonn, Germany.
9
Radboud Institute for Molecular Sciences (RILMS), Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Germany.
10
Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil. Electronic address: fatimardias@gmail.com.
11
Radboud Institute for Molecular Sciences (RILMS), Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil. Electronic address: leo.joosten@radboudumc.nl.

Abstract

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.

KEYWORDS:

BCG; IL-32; IL-32 transgenic mouse; Leishmania braziliensis; proinflammatory cytokines; trained immunity; β-glucan

PMID:
31484076
DOI:
10.1016/j.celrep.2019.08.004
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