Systemic inflammatory response syndrome triggered by blood-borne pathogens induces prolonged dendritic cell paralysis and immunosuppression.

CP: Immunology T cells antigen presentation cell development cross-presentation immunosuppression infection inflammation malaria phagocytosis spatiotemporal adaptations

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
13 Feb 2024
Historique:
received: 04 07 2023
revised: 01 12 2023
accepted: 22 01 2024
medline: 14 2 2024
pubmed: 14 2 2024
entrez: 14 2 2024
Statut: aheadofprint

Résumé

Blood-borne pathogens can cause systemic inflammatory response syndrome (SIRS) followed by protracted, potentially lethal immunosuppression. The mechanisms responsible for impaired immunity post-SIRS remain unclear. We show that SIRS triggered by pathogen mimics or malaria infection leads to functional paralysis of conventional dendritic cells (cDCs). Paralysis affects several generations of cDCs and impairs immunity for 3-4 weeks. Paralyzed cDCs display distinct transcriptomic and phenotypic signatures and show impaired capacity to capture and present antigens in vivo. They also display altered cytokine production patterns upon stimulation. The paralysis program is not initiated in the bone marrow but during final cDC differentiation in peripheral tissues under the influence of local secondary signals that persist after resolution of SIRS. Vaccination with monoclonal antibodies that target cDC receptors or blockade of transforming growth factor β partially overcomes paralysis and immunosuppression. This work provides insights into the mechanisms of paralysis and describes strategies to restore immunocompetence post-SIRS.

Identifiants

DOI: 10.1016/j.celrep.2024.113754 PMID: 38354086
pubmed: 38354086
pii: S2211-1247(24)00082-2
doi: 10.1016/j.celrep.2024.113754
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

113754

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests M.H.L., I.C., and K.S. are listed as inventors on patents relating to Clec9A antibodies.

Auteurs

Mitra Ashayeripanah (M)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC 3000, Australia.

Javier Vega-Ramos (J)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC 3000, Australia; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.

Daniel Fernandez-Ruiz (D)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC 3000, Australia; School of Biomedical Sciences, Faculty of Medicine & Health and the UNSW RNA Institute, The University of New South Wales, Kensington, NSW 2052, Australia.

Shirin Valikhani (S)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC 3000, Australia.

Aaron T L Lun (ATL)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.

Jason T White (JT)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC 3000, Australia.

Louise J Young (LJ)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.

Atefeh Yaftiyan (A)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC 3000, Australia.

Yifan Zhan (Y)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.

Linda Wakim (L)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC 3000, Australia.

Irina Caminschi (I)

Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.

Mireille H Lahoud (MH)

Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.

Andrew M Lew (AM)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.

Ken Shortman (K)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.

Gordon K Smyth (GK)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Mathematics and Statistics, The University of Melbourne, Parkville, VIC 3010, Australia.

William R Heath (WR)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC 3000, Australia.

Justine D Mintern (JD)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia.

Antoine Roquilly (A)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC 3000, Australia; Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, 44000 Nantes, France; CHU Nantes, INSERM, Nantes Université, Anesthesie Reanimation, CIC 1413, 44000 Nantes, France. Electronic address: antoine.roquilly@chu-nantes.fr.

Jose A Villadangos (JA)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC 3000, Australia; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: j.villadangos@unimelb.edu.au.

Classifications MeSH