GM-CSF Programs Hematopoietic Stem and Progenitor Cells During Candida albicans Vaccination for Protection Against Reinfection

More mechanistic studies are needed to reveal the hidden details of -induced trained immunity. Here, using a live vaccine mouse model we show that vaccination protects mice against a secondary infection and increases the number of bone marrow, and especially, splenic trained monocytes. Moreover, vac...

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Published inFrontiers in immunology Vol. 12; p. 790309
Main Authors Bono, Cristina, Guerrero, Paula, Jordán-Pla, Antonio, Erades, Ana, Salomonis, Nathan, Grimes, H Leighton, Gil, M Luisa, Yáñez, Alberto
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 15.12.2021
Subjects
Animals
Candida albicans - immunology
candidiasis
Candidiasis - prevention & control
Cytokines - biosynthesis
Female
Fungal Vaccines - immunology
GM-CSF
Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology
Hematopoietic Stem Cells - drug effects
Hematopoietic Stem Cells - physiology
HSPCs
Immunology
Macrophages - physiology
Male
Mice
Mice, Inbred C57BL
Myelopoiesis
Reinfection - prevention & control
trained immunity
Vaccination
HSPCs
candidiasis
trained immunity
GM-CSF
myelopoiesis
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Summary:More mechanistic studies are needed to reveal the hidden details of -induced trained immunity. Here, using a live vaccine mouse model we show that vaccination protects mice against a secondary infection and increases the number of bone marrow, and especially, splenic trained monocytes. Moreover, vaccination expands and reprograms hematopoietic stem and progenitor cells (HSPCs) early during infection and mobilize them transiently to the spleen to produce trained macrophages. Trained HSPCs are not only primed for myeloid cell production but also reprogramed to produce a greater amount of proinflammatory cytokines in response to a second challenge. Additionally, their adoptive transfer is sufficient to protect mice against reinfection. Mechanistically, autocrine GM-CSF activation of HSPCs is responsible for the trained phenotype and essential for the vaccine-induced protection. Our findings reveal a fundamental role for HSPCs in the trained immune protective response, opening new avenues for disease prevention and treatment.
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This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology
Reviewed by: Nobuyuki Onai, Kanazawa Medical University, Japan; Yasutaka Okabe, Osaka University, Japan
Edited by: Eric Pearlman, University of California, Irvine, United States
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.790309