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Neutrophils in People Living With HIV-1 on antiretroviral treatment conserve their cytokine and chemokine secretion capacity and display enhanced expression of Fc receptors
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Neutrophils in People Living With HIV-1 on antiretroviral treatment conserve their cytokine and chemokine secretion capacity and display enhanced expression of Fc receptors
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Paper
Neutrophils in People Living With HIV-1 on antiretroviral treatment conserve their cytokine and chemokine secretion capacity and display enhanced expression of Fc receptors
2024
Overview
Neutrophils are innate immune cells that display immunomodulatory properties by secreting cytokines and chemokines. By using a mouse model of retroviral infection, we previously uncovered the key immunomodulatory function of neutrophils in promoting protective immunity during antiviral antibody therapy which occurs in a Fc-dependent manner. Here, we investigated the immunomodulatory properties of neutrophils in the context of HIV-1 infection and therapy. We characterized the functional activation and the modulation of Fcγ receptors (FcγRs) expression on neutrophils isolated from healthy donors (HD) or people living with HIV-1 (PLWH) upon stimulation with virions, free or in the form of immune complexes (ICs) made with broadly neutralizing antibodies (bNAbs). Neutrophils from HD secreted cytokines/chemokines in small amount upon activation by either stimulus. Interestingly, conditioning of neutrophils from HD with pro-inflammatory cytokines enhanced their cytokine/chemokine production upon activation by HIV-1 and ICs, highlighting that the inflammatory environment is key for neutrophils to show a functional response to these stimuli. Noteworthy, under inflammatory conditions, IC-activated neutrophils showed higher secretion of CXCL1 and CCL4 than HIV-1-stimulated neutrophils. Importantly, neutrophils from PLWH on antiretroviral treatment (ART) maintained their cytokine/chemokine secretion abilities when stimulated by TLR agonists, TNFα; or HIV-1/ICs. However, they displayed different phenotypic features as compared with neutrophils isolated from HD, notably higher expression of FcγRs. Our study provides new insights into the immunomodulatory properties of neutrophils during HIV-1 infection and therapy. This might contribute to the improvement of antiviral antibody therapies through the use of therapeutic approaches exploiting the immunomodulatory properties of these cells.Competing Interest StatementThe authors have declared no competing interest.
Publisher
Cold Spring Harbor Laboratory Press
