Responses of monocytes to TLR ligands during primary HIV-1 infection

Abstract

Objective To investigate the maturation status of monocytes and their responses to the stimulation of toll like receptor （TLR） ligands during primary HIV-1 infection, and to further understand the correlation between functional status of monocytes and disease progression during primary HIV -1 infection. Methods Peripheral blood mononuclear cells （ PBMCs） were collected from 35 subjects with primary HIV-1 infection and 13 HIV-negative healthy subjects to isolate monocytes .Monocytes were stimulated with LPS and Pam3CSK4, respectively, and cultured for 20 hours.The expression of activaion/inhibitory markers on monocytes were analyzed by flow cytometry before and after stimulation .The secretion of proinflammatory cy-tokines （ IL-1β, TNF-αand IL-6） by stimulated monocytes were detected by ELISA .Results The expres-sion of activation markers CD80, CD86, CD40 and inhibitory marker PD-L1 on monocytes were increased in subjects with primary HIV-1 infection （P〈0.001 except for CD86 P=0.01）.The level of CD40 was posi-tively correlated with viral load in plasma （P〈0.001, R=0.553）.Compared with control group, primary HIV-1 infection group showed a less increase in the expression of HLA-DR, CD80, CD86 and PD-L1 on monocytes after stimulation with LPS and Pam3CSK4 （P〈0.001）, but the secretion of proinflammatory cyto-kines TNF-α（LPS：P=0.004, Pam3CSK4：P=0.012） and IL-6 （LPS：P=0.006） were enhanced in mono-cytes from patients with primary HIV-1 infection.Conclusion Monocytes were activated during primary HIV-1 infection.They secreted higher level of proinflammatory cytokines after stimulation with TLR ligands , indicating monocytes might play a role in microbial translocation and immune activation during HIV -1 infection . Key words: Human immunodeficiency virus; Monocytes