Diminished FcγRIIa expression reduces antibody-mediated phagocytosis by low-density neutrophils in obesity

Abstract Obesity is a chronic inflammatory disease associated with an increased risk of various medical complications, including cardiovascular problems, diabetes, and infectious diseases. A central element of the immune system associated with inflammation and antimicrobial function is neutrophils. Recently, distinct neutrophil subpopulations have been described in different conditions. One neutrophil subpopulation, the low-density neutrophils (LDN), is of particular interest because LDN numbers increase significantly in several diseases. However, in the context of obesity, there is little information on the appearance and functions of LDN. Therefore, to evaluate whether LDN numbers increase in individuals with obesity and to explore their functional properties, LDN from individuals with normal weight and from individuals with obesity were isolated, and their phenotypes and microbicidal functions were assessed. In individuals with normal weight, LDN showed enhanced respiratory burst and more efficient antibody-mediated phagocytosis than neutrophils. In individuals with obesity, LDN numbers were elevated. However, in these LDN, phagocytosis and NETosis were impaired. Also, LDN from individuals with obesity had lower expression of the phagocytic receptor FcγRIIa. In addition, although LDN from cancer patients have been reported to be immunosuppressive, LDN either from individuals with normal weight or from individuals with obesity did not inhibit the proliferation of T-cells. Together, these findings suggest that obesity induces elevated numbers of LDN. But, these LDN perform phagocytosis and NETosis less efficiently than LDN from individuals with normal weight. This deficiency could explain, in part, the increased disease severity of infections observed in individuals with obesity.