Dectin-1 Stimulation of Hematopoietic Stem and Progenitor Cells Occurs <italic toggle="yes">In Vivo</italic> and Promotes Differentiation Toward Trained Macrophages via an Indirect Cell-Autonomous Mechanism

ABSTRACT Toll-like receptor (TLR) agonists drive hematopoietic stem and progenitor cells (HSPCs) to differentiate along the myeloid lineage. In this study, we used an HSPC transplantation model to investigate the possible direct interaction of β-glucan and its receptor (dectin-1) on HSPCs in vivo. P...

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Autores principales:	Cristina Bono, Alba Martínez, Javier Megías, Daniel Gozalbo, Alberto Yáñez, M. Luisa Gil
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	hematopoietic stem and progenitor cells Candida albicans dectin-1 TLR2 macrophages trained immunity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/90c81f4ab487455ba7308d7bcd3405ae
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spelling	oai:doaj.org-article:90c81f4ab487455ba7308d7bcd3405ae2021-11-15T15:56:46ZDectin-1 Stimulation of Hematopoietic Stem and Progenitor Cells Occurs <italic toggle="yes">In Vivo</italic> and Promotes Differentiation Toward Trained Macrophages via an Indirect Cell-Autonomous Mechanism10.1128/mBio.00781-202150-7511https://doaj.org/article/90c81f4ab487455ba7308d7bcd3405ae2020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00781-20https://doaj.org/toc/2150-7511ABSTRACT Toll-like receptor (TLR) agonists drive hematopoietic stem and progenitor cells (HSPCs) to differentiate along the myeloid lineage. In this study, we used an HSPC transplantation model to investigate the possible direct interaction of β-glucan and its receptor (dectin-1) on HSPCs in vivo. Purified HSPCs from bone marrow of B6Ly5.1 mice (CD45.1 alloantigen) were transplanted into dectin-1−/− mice (CD45.2 alloantigen), which were then injected with β-glucan (depleted zymosan). As recipient mouse cells do not recognize the dectin-1 agonist injected, interference by soluble mediators secreted by recipient cells is negligible. Transplanted HSPCs differentiated into macrophages in response to depleted zymosan in the spleens and bone marrow of recipient mice. Functionally, macrophages derived from HSPCs exposed to depleted zymosan in vivo produced higher levels of inflammatory cytokines (tumor necrosis factor alpha [TNF-α] and interleukin 6 [IL-6]). These results demonstrate that trained immune responses, already described for monocytes and macrophages, also take place in HSPCs. Using a similar in vivo model of HSPC transplantation, we demonstrated that inactivated yeasts of Candida albicans induce differentiation of HSPCs through a dectin-1- and MyD88-dependent pathway. Soluble factors produced following exposure of HSPCs to dectin-1 agonists acted in a paracrine manner to induce myeloid differentiation and to influence the function of macrophages derived from dectin-1-unresponsive or β-glucan-unexposed HSPCs. Finally, we demonstrated that an in vitro transient exposure of HSPCs to live C. albicans cells, prior to differentiation, is sufficient to induce a trained phenotype of the macrophages they produce in a dectin-1- and Toll-like receptor 2 (TLR2)-dependent manner. IMPORTANCE Invasive candidiasis is an increasingly frequent cause of serious and often fatal infections. Understanding host defense is essential to design novel therapeutic strategies to boost immune protection against Candida albicans. In this article, we delve into two new concepts that have arisen over the last years: (i) the delivery of myelopoiesis-inducing signals by microbial components directly sensed by hematopoietic stem and progenitor cells (HSPCs) and (ii) the concept of “trained innate immunity” that may also apply to HSPCs. We demonstrate that dectin-1 ligation in vivo activates HSPCs and induces their differentiation to trained macrophages by a cell-autonomous indirect mechanism. This points to new mechanisms by which pathogen detection by HSPCs may modulate hematopoiesis in real time to generate myeloid cells better prepared to deal with the infection. Manipulation of this process may help to boost the innate immune response during candidiasis.Cristina BonoAlba MartínezJavier MegíasDaniel GozalboAlberto YáñezM. Luisa GilAmerican Society for Microbiologyarticlehematopoietic stem and progenitor cellsCandida albicansdectin-1TLR2macrophagestrained immunityMicrobiologyQR1-502ENmBio, Vol 11, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	hematopoietic stem and progenitor cells Candida albicans dectin-1 TLR2 macrophages trained immunity Microbiology QR1-502
spellingShingle	hematopoietic stem and progenitor cells Candida albicans dectin-1 TLR2 macrophages trained immunity Microbiology QR1-502 Cristina Bono Alba Martínez Javier Megías Daniel Gozalbo Alberto Yáñez M. Luisa Gil Dectin-1 Stimulation of Hematopoietic Stem and Progenitor Cells Occurs <italic toggle="yes">In Vivo</italic> and Promotes Differentiation Toward Trained Macrophages via an Indirect Cell-Autonomous Mechanism
description	ABSTRACT Toll-like receptor (TLR) agonists drive hematopoietic stem and progenitor cells (HSPCs) to differentiate along the myeloid lineage. In this study, we used an HSPC transplantation model to investigate the possible direct interaction of β-glucan and its receptor (dectin-1) on HSPCs in vivo. Purified HSPCs from bone marrow of B6Ly5.1 mice (CD45.1 alloantigen) were transplanted into dectin-1−/− mice (CD45.2 alloantigen), which were then injected with β-glucan (depleted zymosan). As recipient mouse cells do not recognize the dectin-1 agonist injected, interference by soluble mediators secreted by recipient cells is negligible. Transplanted HSPCs differentiated into macrophages in response to depleted zymosan in the spleens and bone marrow of recipient mice. Functionally, macrophages derived from HSPCs exposed to depleted zymosan in vivo produced higher levels of inflammatory cytokines (tumor necrosis factor alpha [TNF-α] and interleukin 6 [IL-6]). These results demonstrate that trained immune responses, already described for monocytes and macrophages, also take place in HSPCs. Using a similar in vivo model of HSPC transplantation, we demonstrated that inactivated yeasts of Candida albicans induce differentiation of HSPCs through a dectin-1- and MyD88-dependent pathway. Soluble factors produced following exposure of HSPCs to dectin-1 agonists acted in a paracrine manner to induce myeloid differentiation and to influence the function of macrophages derived from dectin-1-unresponsive or β-glucan-unexposed HSPCs. Finally, we demonstrated that an in vitro transient exposure of HSPCs to live C. albicans cells, prior to differentiation, is sufficient to induce a trained phenotype of the macrophages they produce in a dectin-1- and Toll-like receptor 2 (TLR2)-dependent manner. IMPORTANCE Invasive candidiasis is an increasingly frequent cause of serious and often fatal infections. Understanding host defense is essential to design novel therapeutic strategies to boost immune protection against Candida albicans. In this article, we delve into two new concepts that have arisen over the last years: (i) the delivery of myelopoiesis-inducing signals by microbial components directly sensed by hematopoietic stem and progenitor cells (HSPCs) and (ii) the concept of “trained innate immunity” that may also apply to HSPCs. We demonstrate that dectin-1 ligation in vivo activates HSPCs and induces their differentiation to trained macrophages by a cell-autonomous indirect mechanism. This points to new mechanisms by which pathogen detection by HSPCs may modulate hematopoiesis in real time to generate myeloid cells better prepared to deal with the infection. Manipulation of this process may help to boost the innate immune response during candidiasis.
format	article
author	Cristina Bono Alba Martínez Javier Megías Daniel Gozalbo Alberto Yáñez M. Luisa Gil
author_facet	Cristina Bono Alba Martínez Javier Megías Daniel Gozalbo Alberto Yáñez M. Luisa Gil
author_sort	Cristina Bono
title	Dectin-1 Stimulation of Hematopoietic Stem and Progenitor Cells Occurs <italic toggle="yes">In Vivo</italic> and Promotes Differentiation Toward Trained Macrophages via an Indirect Cell-Autonomous Mechanism
title_short	Dectin-1 Stimulation of Hematopoietic Stem and Progenitor Cells Occurs <italic toggle="yes">In Vivo</italic> and Promotes Differentiation Toward Trained Macrophages via an Indirect Cell-Autonomous Mechanism
title_full	Dectin-1 Stimulation of Hematopoietic Stem and Progenitor Cells Occurs <italic toggle="yes">In Vivo</italic> and Promotes Differentiation Toward Trained Macrophages via an Indirect Cell-Autonomous Mechanism
title_fullStr	Dectin-1 Stimulation of Hematopoietic Stem and Progenitor Cells Occurs <italic toggle="yes">In Vivo</italic> and Promotes Differentiation Toward Trained Macrophages via an Indirect Cell-Autonomous Mechanism
title_full_unstemmed	Dectin-1 Stimulation of Hematopoietic Stem and Progenitor Cells Occurs <italic toggle="yes">In Vivo</italic> and Promotes Differentiation Toward Trained Macrophages via an Indirect Cell-Autonomous Mechanism
title_sort	dectin-1 stimulation of hematopoietic stem and progenitor cells occurs <italic toggle="yes">in vivo</italic> and promotes differentiation toward trained macrophages via an indirect cell-autonomous mechanism
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/90c81f4ab487455ba7308d7bcd3405ae
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Dectin-1 Stimulation of Hematopoietic Stem and Progenitor Cells Occurs <italic toggle="yes">In Vivo</italic> and Promotes Differentiation Toward Trained Macrophages via an Indirect Cell-Autonomous Mechanism

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