Fc receptors are key discriminatory markers of granulocytes subsets in people living with HIV-1.

Introduction: Granulocytes are innate immune cells that play a key role in pathogen elimination. Recent studies revealed the diversity of granulocytes in terms of phenotype and function. In particular, a subset of granulocytes identified as low-density granulocytes (LDG) has been described in physiological conditions and with increased frequencies in several pathological contexts. However, the properties of LDG are still controversial as they vary according to the pathophysiological environment. Here we investigated the heterogeneity of granulocyte populations and the potential differences in phenotype and immunomodulatory capacity between LDG and normal density granulocytes (NDG) in people living with HIV-1 (PLWH). Methods: To this end, we developed an optimized method to purify LDG and NDG from a single blood sample, and performed in-depth, comparative phenotypic characterization of both granulocyte subtypes. We also assessed the impact of purification steps on the expression of cell surface markers on LDG by immunophenotyping them at different stages of isolation. Results: We identified 9 cell surface markers (CD16, CD32, CD89, CD62L, CD177, CD31, CD10, CXCR4 and CD172α) differentially expressed between LDG and NDG. Noteworthy, markers that distinguish the two subsets include receptors for the Fc part of IgG (CD16, CD32) and IgA (CD89). Importantly, we also highlighted that the purification procedure affects the expression of several cell surface markers (i.e.CD63, CD66b, …) which must be taken into account when characterizing LDG. Our work sheds new light on the properties of LDG in PLWH and provides an extensive characterization of this granulocyte subset in which Fc receptors are key discriminatory markers.

Fc-Dependent Immunomodulation Induced by Antiviral Therapeutic Antibodies: New Perspectives for Eliciting Protective Immune Responses.

The multiple mechanisms of action of antiviral monoclonal antibodies (mAbs) have made these molecules a potential therapeutic alternative for treating severe viral infections. In addition to their direct effect on viral propagation, several studies have shown that mAbs are able to enhance the host's adaptive immune response and generate long-lasting protective immunity. Such immunomodulatory effects occur in an Fc-dependent manner and rely on Fc-FcγR interactions. It is noteworthy that several FcγR-expressing cells have been shown to play a key role in enhancing humoral and cellular immune responses (so-called "vaccinal effects") in different experimental settings. This review recalls recent findings concerning the vaccinal effects induced by antiviral mAbs, both in several preclinical animal models and in patients treated with mAbs. It summarizes the main cellular and molecular mechanisms involved in these immunomodulatory properties of antiviral mAbs identified in different pathological contexts. It also describes potential therapeutic interventions to enhance host immune responses that could guide the design of improved mAb-based immunotherapies.