CD300a inhibits CD16-mediated NK cell effector functions in HIV-1-infected patients

Abstract

Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) through CD16 has a critical role in anti-human immunodeficiency virus (HIV) responses. CD300a, an inhibitory receptor highly expressed on NK cells, has the capacity to diminish NK cell killing of pseudorabies-infected cells. CD300a expression is altered during HIV-1 infection on B cells and CD4+ T lymphocytes. In this work, we have investigated in a cross-sectional study the expression and function of CD300a on NK cells from healthy donors, untreated HIV-1 infected subjects and patients on combined antiretroviral treatment (cART). First, we detected an expansion of a CD300a-expressing CD56neg NK cell subset in untreated HIV-1 infected patients. In addition, an association between CD300a expression and other NK cell surface receptors was observed in both healthy and HIV-1 infected people. Notably, we also described that CD300a exerted an inhibitory effect in CD16-mediated effector functions, including degranulation and cytokine production, in all donors and NK cell subsets and, more importantly, this inhibitory effect was higher in HIV-1 infected patients. Therefore, the CD300a inhibitory receptor could be proposed as a new target for therapies aimed to improve NK cells effector functions in HIV-1 infected patients.