The Study Of Monocytes Subsets,Phenotype And Function During HIV-1 Infection

Objective: Monocyte activation is thought to contribute to persistent immune activation in the HIV-1-infected individuals.In 2010,monocytes have been recently subdivided into three subsets by the Nomenclature Committee of the International Union of Immunological Societies: classical(CD14++CD16-),intermediate(CD14++CD16+)and non-classical(CD14+CD16++)subsets.The phenotypic and functional abnormalities of the three monocyte subsets in HIV-1 infection have not been fully characterized,especially in acute HIV-1 infection.Methods: Thirty-seven homosexual men with acute HIV-1 infection patients,31 chronic cART-na?ve HIV-1-infected patients,63 chronic HIV-1-infected patients with cART,and 42 Health control were enrolled in the study,the ages of all groups were matched.Blood samples were collected.In this study,we explored the dynamic changes of monocyte subsets and their surface markers in acute,chronic HIV-1-infected patients and the patients in cART.Intracellular IFN-γ,IL-4,IL-17 and TNF-α staining was performed using peripheral blood mononuclear cells after stimulation with PMA,ionomycin and brefeldin A for 5 hours,and we evaluated the association between monocyte subsets and helper T cells differentiation.Soluble CD163 in plasma was measured using ELISA.Results: We found that the HLA-DR expression on intermediate CD14++CD16+ monocytes in acute HIV-1 infection was higher than that in both healthy controls and chronic HIV-1 infection.Intermediate CD14++CD16+ monocyte subsets and their HLA-DR expression levels were inversely correlated with the CD4/CD8 ratio,and the intermediate CD14++CD16+ monocytes were positively correlated with plasma sCD163.In contrast to the non-classical CD14+CD16++ and classical CD14++CD16-monocyte subsets,the frequency of the intermediate CD14++CD16+ monocytes was positively associated with the frequency of IFN-γ and IL-4 producing CD4+ T cells.Conclusions: The frequency,phenotypic and functional abnormalities of the three monocyte subsets existed despite suppression of HIV-1 after combined antiretroviral therapy.The abnormalities of intermediate CD14++CD16+ monocytes may affect the immune status in acute HIV-1-infected patients.The frequency of intermediate CD14++CD16+ monocytes subset continued to rise whether to receive cART during HIV-1 infection,and intermediate CD14++CD16+ monocytes subset correlated with disease progression in acute and chronic HIV-1-infected individuals.The frequencies of intermediate CD14++CD16+ monocytes subset and plasma sCD163 level continuously elevated are related to chronic immune activation during HIV-1 infection.Our observations provide new insight into the roles of the monocyte subsets in HIV-1 pathogenesis,and our findings may be helpful for the treatment of HIV-1-related chronic immune activation.