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Communication

TLR2 and Dectin-1 Signaling in Mouse Hematopoietic Stem and Progenitor Cells Impacts the Ability of the Antigen Presenting Cells They Produce to Activate CD4 T Cells

1
Departamento de Microbiología y Ecología, and Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), Universitat de València, 46100 Burjassot, Spain
2
Board of Governors Regenerative Medicine Institute, and Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
*
Author to whom correspondence should be addressed.
Cells 2020, 9(5), 1317; https://doi.org/10.3390/cells9051317
Submission received: 7 April 2020 / Revised: 19 May 2020 / Accepted: 22 May 2020 / Published: 25 May 2020
(This article belongs to the Special Issue Dendritic Cells in Immunity and Inflammation)

Abstract

Microbial recognition by pattern recognition receptors (PRRs) expressed on hematopoietic stem and progenitor cells (HSPCs) not only activates myelopoiesis but also programs the function of the monocytes and macrophages they produce. For instance, changes in HSPC programming modify the ability of macrophages derived from them to produce inflammatory cytokines. While HSPCs exposed to a TLR2 agonist give rise to tolerized macrophages (lower proinflammatory cytokine production), HSPCs treated with Dectin-1 ligands produce trained macrophages (higher proinflammatory cytokine production). However, nothing is known about the impact of HSPC exposure to microbes on the function of antigen presenting cells (APCs). In this study we evaluated whether treatment of murine bone marrow HSPCs with a TLR2 or Dectin-1 ligand impacts the antigen presenting capacity of APCs derived from them in vitro. Following activation with microbial ligands or Candida albicans yeasts, APCs derived from TLR2/Dectin-1-programed HSPCs exhibit altered expression of MHCII (signal 1), co-stimulatory molecules (CD40, CD80 and CD86; signal 2) and cytokines (TNF-α, IL-6, IL-12 p40 and IL-2; signal 3). Moreover, APCs derived from TLR2/Dectin-1-programed HSPCs prime enhanced Th1 and Th17 responses, which are important for antifungal defense, in CD4 T cell cocultures. Overall, these results demonstrate for the first time that microbial detection by bone marrow HSPCs can modulate the adaptive immune response by inducing the production of APCs with an altered phenotype.
Keywords: hematopoietic stem and progenitor cells; TLR2; Dectin-1; antigen presenting cells; CD4 T cells; innate immune memory hematopoietic stem and progenitor cells; TLR2; Dectin-1; antigen presenting cells; CD4 T cells; innate immune memory

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MDPI and ACS Style

Martínez, A.; Bono, C.; Gozalbo, D.; Goodridge, H.S.; Gil, M.L.; Yáñez, A. TLR2 and Dectin-1 Signaling in Mouse Hematopoietic Stem and Progenitor Cells Impacts the Ability of the Antigen Presenting Cells They Produce to Activate CD4 T Cells. Cells 2020, 9, 1317. https://doi.org/10.3390/cells9051317

AMA Style

Martínez A, Bono C, Gozalbo D, Goodridge HS, Gil ML, Yáñez A. TLR2 and Dectin-1 Signaling in Mouse Hematopoietic Stem and Progenitor Cells Impacts the Ability of the Antigen Presenting Cells They Produce to Activate CD4 T Cells. Cells. 2020; 9(5):1317. https://doi.org/10.3390/cells9051317

Chicago/Turabian Style

Martínez, Alba, Cristina Bono, Daniel Gozalbo, Helen S. Goodridge, M. Luisa Gil, and Alberto Yáñez. 2020. "TLR2 and Dectin-1 Signaling in Mouse Hematopoietic Stem and Progenitor Cells Impacts the Ability of the Antigen Presenting Cells They Produce to Activate CD4 T Cells" Cells 9, no. 5: 1317. https://doi.org/10.3390/cells9051317

APA Style

Martínez, A., Bono, C., Gozalbo, D., Goodridge, H. S., Gil, M. L., & Yáñez, A. (2020). TLR2 and Dectin-1 Signaling in Mouse Hematopoietic Stem and Progenitor Cells Impacts the Ability of the Antigen Presenting Cells They Produce to Activate CD4 T Cells. Cells, 9(5), 1317. https://doi.org/10.3390/cells9051317

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