Article (Scientific journals)
Ly6Chi monocytes balance regulatory and cytotoxic CD4 T cell responses to control virus-induced immunopathology.
Maquet, Céline; Baiwir, Jérôme; Loos, Pauline et al.
2022In Science Immunology, 7 (73), p. 3240
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Keywords :
Animals; Mice; T-Lymphocytes, Cytotoxic; CD4-Positive T-Lymphocytes; Monocytes; Immunology
Abstract :
[en] Gammaherpesviruses (γHVs) have coevolved with their host, leading to a remarkably high infection prevalence and establishment of latency. The lifelong persistence of γHVs in hosts appears to broadly shape host immunity, and we show here that pulmonary infection with Murid herpesvirus 4 (MuHV-4), a mouse γHV, drives the recruitment of Ly6Chi monocytes (MOs) into the airway, thereby modulating the host immune response. The absence of Ly6Chi MOs is associated with severe virus-induced immunopathology and the systemic release of inflammatory mediators. Mechanistically, MuHV-4-imprinted MOs recruit CD4 T cells to the airways and trigger immunosuppressive signaling pathways through the PD-L1/PD-1 axis, thereby dampening the deleterious activation of cytotoxic CD4 T cells. These results uncover a role for Ly6Chi MOs in modulating CD4 T cell functions and reveal pathways that could be targeted therapeutically to reduce detrimental immunopathological responses associated with respiratory viral infections.
Disciplines :
Immunology & infectious disease
Author, co-author :
Maquet, Céline  ;  Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH)
Baiwir, Jérôme  ;  Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH)
Loos, Pauline  ;  Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH)
Rodriguez Rodriguez, Lucia  ;  Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Javaux, Justine ;  Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Sandor, Rémy ;  Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Perin, Fabienne ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Fallon, Padraic G ;  School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
Mack, Matthias;  Department of Nephrology, University Hospital Regensburg, Regensburg, Germany
Cataldo, Didier  ;  Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Gillet, Laurent   ;  Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Machiels, Bénédicte   ;  Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI)
 These authors have contributed equally to this work.
Language :
English
Title :
Ly6Chi monocytes balance regulatory and cytotoxic CD4 T cell responses to control virus-induced immunopathology.
Publication date :
15 July 2022
Journal title :
Science Immunology
eISSN :
2470-9468
Publisher :
NLM (Medline), United States
Volume :
7
Issue :
73
Pages :
eabn3240
Peer reviewed :
Peer Reviewed verified by ORBi
Funding text :
ERC-2019-STG - VIROME - 853608
Available on ORBi :
since 08 September 2022

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