Header

UZH-Logo

Maintenance Infos

Non-neutralizing antibodies protect against chronic LCMV infection by promoting infection of inflammatory monocytes in mice


Stoycheva, Diana; Sandu, Ioana; Gräbnitz, Fabienne; Amorim, Ana; Borsa, Mariana; Weber, Stefan; Becher, Burkhard; Oxenius, Annette (2021). Non-neutralizing antibodies protect against chronic LCMV infection by promoting infection of inflammatory monocytes in mice. European Journal of Immunology, 51(6):1423-1435.

Abstract

Antibodies play an important role in host defense against microorganisms. Besides direct microbicidal activities, antibodies can also provide indirect protection via crosstalk to constituents of the adaptive immune system. Similar to many human chronic viral infections, persistence of Lymphocytic choriomeningitis virus (LCMV) is associated with compromised T- and B-cell responses. The administration of virus-specific non-neutralizing antibodies (nnAbs) prior to LCMV infection protects against the establishment of chronic infection. Here, we show that LCMV-specific nnAbs bind preferentially Ly6C$^{hi}$ inflammatory monocytes (IMs), promote their infection in an Fc-receptor independent way, and support acquisition of APC properties. By constituting additional T-cell priming opportunities, IMs promote early activation of virus-specific CD8 T cells, eventually tipping the balance between T-cell exhaustion and effector cell differentiation, preventing establishment of viral persistence without causing lethal immunopathology. These results document a beneficial role of IMs in avoiding T-cell exhaustion and an Fc-receptor independent protective mechanism provided by LCMV-specific nnAbs against the establishment of chronic infection.

Abstract

Antibodies play an important role in host defense against microorganisms. Besides direct microbicidal activities, antibodies can also provide indirect protection via crosstalk to constituents of the adaptive immune system. Similar to many human chronic viral infections, persistence of Lymphocytic choriomeningitis virus (LCMV) is associated with compromised T- and B-cell responses. The administration of virus-specific non-neutralizing antibodies (nnAbs) prior to LCMV infection protects against the establishment of chronic infection. Here, we show that LCMV-specific nnAbs bind preferentially Ly6C$^{hi}$ inflammatory monocytes (IMs), promote their infection in an Fc-receptor independent way, and support acquisition of APC properties. By constituting additional T-cell priming opportunities, IMs promote early activation of virus-specific CD8 T cells, eventually tipping the balance between T-cell exhaustion and effector cell differentiation, preventing establishment of viral persistence without causing lethal immunopathology. These results document a beneficial role of IMs in avoiding T-cell exhaustion and an Fc-receptor independent protective mechanism provided by LCMV-specific nnAbs against the establishment of chronic infection.

Statistics

Citations

Dimensions.ai Metrics
5 citations in Web of Science®
4 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 18 Nov 2021
13 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Language:English
Date:June 2021
Deposited On:18 Nov 2021 07:06
Last Modified:25 Feb 2024 02:48
Publisher:Wiley-VCH Verlag
ISSN:0014-2980
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/eji.202049068
PubMed ID:33547634
  • Content: Published Version
  • Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)