Journal Article
. 2021 Apr; 10(1):964-981.
doi: 10.1080/22221751.2021.1913068.

Differential and sequential immunomodulatory role of neutrophils and Ly6Chi inflammatory monocytes during antiviral antibody therapy

Jennifer Lambour 1 Mar Naranjo-Gomez 1 Myriam Boyer-Clavel 2 Mireia Pelegrin 1 
Affiliations
  • PMID: 33858301
  •     64 References

Abstract

Antiviral monoclonal antibodies (mAbs) can generate protective immunity through Fc-FcγRs interactions. We previously showed a role for immune complexes (ICs) in the enhancement of antiviral T-cell responses through FcγR-mediated activation of dendritic cells (DCs). Here we addressed how mAb therapy in retrovirus-infected mice affects the activation of neutrophils and inflammatory monocytes, two FcγR-expressing innate effector cells rapidly recruited to sites of infection. We found that both cell-types activated in vitro by viral ICs secreted chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced FcγRIV upregulation. Similarly, infection and mAb-treatment upregulated FcγRIV on neutrophils and inflammatory monocytes and enhanced their cytokines/chemokines secretion. Notably, upon antibody therapy neutrophils and inflammatory monocytes displayed distinct functional activation states and sequentially modulated the antiviral immune response by secreting Th1-type polarizing cytokines and chemokines, which occurred in a FcγRIV-dependent manner. Consistently, FcγRIV- blocking in mAb-treated, infected mice led to reduced immune protection. Our work provides new findings on the immunomodulatory role of neutrophils and monocytes in the enhancement of immune responses upon antiviral mAb therapy.

Keywords: Antiviral immune responses; FcγR; immune complexes; immunotherapy; monoclonal antibodies; monocytes; neutrophils; vaccinal effects.

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