Sepsis expands a CD39 + plasmablast population that promotes immunosuppression via adenosine-mediated inhibition of macrophage antimicrobial activity
| Autor: | Paulo Henrique Melo, Luisa Menezes-Silva, Fernando Q. Cunha, Marcos C. Borges, Bernhard Ryffel, Daniel Zoppi, Ícaro Maia Santos de Castro, Juliana E Toller-Kawahisa, Diego B. Caetite, Paula Ramos Viacava, Antonio Edson Rocha Oliveira, Raphael S. Peres, Helder I. Nakaya, Daniele C. Nascimento, Joel Linden, Thiago M. Cunha, Dario S. Zamboni, Gilles Kauffenstein, José C. Alves-Filho, Raphael Gomes Ferreira, Valérie F. J. Quesniaux, Denise Morais da Fonseca, Flávio P. Veras, Paula B. Donate, Annie R. Piñeros, Jonas Augusto Rizzato Paschoal, Marina Alves Damaceno |
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| Přispěvatelé: | Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO) |
| Rok vydání: | 2021 |
| Předmět: |
MACRÓFAGOS
[SDV]Life Sciences [q-bio] Secondary infection medicine.medical_treatment Immunology Population Biology Sepsis 03 medical and health sciences 0302 clinical medicine Immune system medicine Immunology and Allergy Macrophage education ComputingMilieux_MISCELLANEOUS 030304 developmental biology B cells 0303 health sciences education.field_of_study immunosuppression Immunosuppression medicine.disease Adenosine macrophages 3. Good health Interleukin 10 Infectious Diseases adenosine 030220 oncology & carcinogenesis plasmablast medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Immunity Immunity, Elsevier, 2021, 54 (9), pp.2024-2041.e8. ⟨10.1016/j.immuni.2021.08.005⟩ |
| ISSN: | 1074-7613 |
| Popis: | Sepsis results in elevated adenosine in circulation. Extracellular adenosine triggers immunosuppressive signaling via the A2a receptor (A2aR). Sepsis survivors develop persistent immunosuppression with increased risk of recurrent infections. We utilized the cecal ligation and puncture (CLP) model of sepsis and subsequent infection to assess the role of adenosine in post-sepsis immune suppression. A2aR-deficient mice showed improved resistance to post-sepsis infections. Sepsis expanded a subset of CD39hi B cells and elevated extracellular adenosine, which was absent in mice lacking CD39-expressing B cells. Sepsis-surviving B cell-deficient mice were more resistant to secondary infections. Mechanistically, metabolic reprogramming of septic B cells increased production of ATP, which was converted into adenosine by CD39 on plasmablasts. Adenosine signaling via A2aR impaired macrophage bactericidal activity and enhanced interleukin-10 production. Septic individuals exhibited expanded CD39hi plasmablasts and adenosine accumulation. Our study reveals CD39hi plasmablasts and adenosine as important drivers of sepsis-induced immunosuppression with relevance in human disease. |
| Databáze: | OpenAIRE |
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