Functionally distinct neutrophils sequentially promote Th1-type responses upon antiviral antibody therapy

Antiviral monoclonal antibodies (mAbs) can generate protective immunity through immune complexes (IC)-FcγRs interactions. We have shown the essential role of neutrophils in mAb-induced immunity of retrovirus-infected mice. Using this model, here we addressed how viral infection, with or without mAb therapy, affects neutrophils’ functional activation. We found that neutrophils activated by viral ICs secreted high levels of chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced FcγRs upregulation. Similarly, infection and mAb-treatment upregulated FcγRs expression on neutrophils and enhanced their cytokines and chemokines secretion. FcγRs upregulation allowed to identify two splenic neutrophils subpopulations with distinct phenotypic and functional properties that differentially and sequentially collaborate with inflammatory monocytes to induce Th1-type responses in mAb-treated mice. Our work provides novel findings on the heterogeneity and the immunomodulatory role of neutrophils in the enhancement of immune responses upon antiviral mAb therapy.