Plasma Phage Load is Positively Related to the Immune Checkpoints in Patients Living with Human Immunodeficiency Virus

Abstract

Background: Microbial Translocation (MT) and altered gut microbiota are involved in immune activation and inflammation, whereas immune checkpoint proteins play an important role in maintaining immune self-tolerance and preventing excessive immune activation.

Objective: This study aims to investigate the relationship between plasma phage load and immune homeostasis in people living with HIV(PLWH).

Methods: We recruited 15 antiretroviral therapy (ART)-naive patients, 23 ART-treated (AT) patients, and 34 Healthy Participants (HP) to explore the relationship between the plasma phage load and immune checkpoint proteins. The Deoxyribonucleic Acid (DNA) load of the lambda (λ) phage was detected using fluorescence quantitative Polymerase Chain Reaction (PCR). The Immune Checkpoints (ICPs) were detected using multiplex immunoassay.

Results: Our study demonstrated that the plasma phage load was increased in people living with HIV (PLWH) (P<0.05), but not in the ART-naive and AT groups (P>0.05). Plasma ICPs, including cluster of differentiation 27 (CD27), soluble glucocorticoid-induced Tumor Necrosis Factor (TNF) receptor (sGITR), soluble cluster of differentiation 80 (sCD80), sCD86, soluble glucocorticoidinduced TNF receptor-related ligand (sGITRL), soluble induced T-cell Costimulatory (sICOS), sCD40, soluble toll-like receptor 2 (sTLR2), and sCD28, were markedly decreased among the ARTnaive group (P<0.05) but not in the AT and HP groups (P>0.05). The plasma phage load was positively correlated with ICP and C-reactive protein (CRP) levels in PLWH (P<0.05).

Conclusion: Our study indicated that the plasma phage load in PLWH was positively related to the expression of ICPs and inflammation, which may be used as a promising marker for the immune level of PLWH.

Keywords: HIV; gut phage translocation; homeostatis; immune checkpoint protein; microbial translocation; plasma phage load.