Distinct inflammation-related proteins associated with T cell immune recovery during chronic HIV-1 infection

ABSTRACT

Chronic inflammation and T cell dysregulation persist in individuals infected with human immunodeficiency virus type 1 (HIV-1), even after successful antiretroviral treatment. The mechanism involved is not fully understood. Here, we used Olink proteomics to comprehensively analyze the aberrant inflammation-related proteins (IRPs) in chronic HIV-1-infected individuals, including in 24 treatment-naïve individuals, 33 immunological responders, and 38 immunological non-responders. T cell dysfunction was evaluated as T cell exhaustion, activation, and differentiation using flow cytometry. We identified a cluster of IRPs (cluster 7), including CXCL11, CXCL9, TNF, CXCL10, and IL18, which was closely associated with T cell dysregulation during chronic HIV-1 infection. Interestingly, IRPs in cluster 5, including ST1A1, CASP8, SIRT2, AXIN1, STAMBP, CD40, and IL7, were negatively correlated with the HIV-1 reservoir size. We also identified a combination of CDCP1, CXCL11, CST5, SLAMF1, TRANCE, and CD5, which may be useful for distinguishing immunological responders and immunological non-responders. In conclusion, the distinct inflammatory milieu is closely associated with immune restoration of T cells, and our results provide insight into immune dysregulation during chronic HIV-1 infection.

KEYWORDS:

• HIV-1
• Inflammation
• HIV-1 reservoir
• CXCL9
• CXCL10
• CXCL11
• T cell dysregulation

Acknowledgements

The authors thank Rui-Chuang Yang, Chun-Bao Zhou, and Jin-Hong Yuan for their excellent technical support with flow cytometry analysis, and we appreciate the efforts of all our team technicians for their hard work throughout this study. JWS and FSW conceived and designed the study. LYW collected clinical samples and performed the experiments with assistance from HHH, BS, WJC, LLS, and MJZ. HHH and BS collected clinical information. LYW, CZ, SYC, and XCZ analyzed data. JWS, FSW, and LYW interpreted data. JWS, LYW, and HHH wrote the manuscript. RNX, XF, JYZ, MS, CZ, and YMJ provided comments and feedback. The order of the co-first authors was assigned based on the relative contributions of the individuals. All authors read and approved the final version before submission.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China [grant numbers 82101837, 81901617], the Natural Science and Technology Major Project [grant number 2018ZX10302104-002-001], the Beijing Natural Science Foundation [grant number 7222171].