TLR2, TLR4 and Dectin-1 signalling in hematopoietic stem and progenitor cells determines the antifungal phenotype of the macrophages they produce

Microbes and Infection
Javier MegíasM Luisa Gil

Abstract

TLRs represent an attractive target for the stimulation of myeloid cell production by HSPCs. We have previously demonstrated that HSPCs use TLR2 to sense Candida albicans in vivo and induce the production of macrophages. In this work, we used an in vitro model of HSPCs differentiation to investigate the functional consequences for macrophages of exposure of HSPCs to various PAMPs and C. albicans cells. Mouse HSPCs (Lin(-) cells) were cultured with M-CSF to induce macrophage differentiation, in the presence or absence of the following PRR agonists: Pam3CSK4 (TLR2 ligand), LPS (TLR4 ligand), depleted zymosan (which only activates Dectin-1), or C. albicans yeasts (which activate several PRRs, but principally TLR2 and Dectin-1). Our data show that these PAMPs differentially impact the anti-microbial function of the macrophages produced by the exposed HSPCs. Pure TLR2 and TLR4 ligands generate macrophages with a diminished ability to produce inflammatory cytokines. In contrast, HSPCs activation in response to C. albicans leads to the generation of macrophages that are better prepared to deal with the infection, as they produce higher amounts of inflammatory cytokines and have higher fungicidal capacity than control macrophages. Ther...Continue Reading

References

Jan 24, 2004·Microbes and Infection·Eva VillamónM Luisa Gil
Mar 11, 2009·Frontiers in Bioscience (Landmark Edition)·Maria Luisa Gil, Daniel Gozalbo
Sep 29, 2009·Trends in Immunology·Subhra K Biswas, Eduardo Lopez-Collazo
Jan 22, 2010·Critical Reviews in Microbiology·Michael A Pfaller, Daniel J Diekema
Jan 15, 2011·Trends in Immunology·Megan T BaldridgeMargaret A Goodell
Mar 12, 2011·Nature Reviews. Immunology·Luigina Romani
Oct 15, 2013·European Journal of Immunology·Alberto YáñezM Luisa Gil

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Citations

Jun 14, 2016·Microbes and Infection·Sophia Häfner
Sep 21, 2018·Frontiers in Cellular and Infection Microbiology·Alba MartínezM Luisa Gil
Feb 2, 2021·Frontiers in Microbiology·Eli Isael MacielNéstor J Oviedo
Dec 21, 2018·Developmental and Comparative Immunology·Eli Isael MacielNéstor J Oviedo
Feb 14, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kyle T CunninghamKingston H G Mills
Jul 24, 2021·Stem Cell Reports·Nir BujanoverRoi Gazit
May 14, 2021·Transplantation·Kyle T Cunningham, Kingston H G Mills
Sep 14, 2021·Stem Cells and Development·Carolina Rodriguez-EcheverriAngel Gonzalez
Dec 4, 2020·Stem Cells·Tobias KoenigerStefanie Kuerten

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