Syphilis Infection Differentially Regulates the Phenotype and Function of γδ T Cells in HIV-1-Infected Patients Depends on the HIV-1 Disease Stage

A rapidly escalating outbreak of syphilis infection has been affected men who have sex with men, particularly those with HIV-1 infection gamma delta T cells are unconventional immune cells with two main subsets, V delta 1 T cells and V delta 2 T cells, which possess a combination of innate and adaptive immune features allowing them against HIV-1. However, whether syphilis infection affects the phenotype and function of gamma delta T cells in HIV-1-infected patients remains unclear, especially in acute HIV-1 infection (AHI). In this study, we enrolled 57 HIV-1-infected patients (24 with HIV-1 infection only and 33 coinfected with syphilis) from an acute HIV-1-infected cohort in Beijing (PRIMO). A comprehensive analysis of gamma delta T-cell phenotype and function was performed by flow cytometry. We found syphilis coinfection could reverse the imbalance of V delta 1/V delta 2 ratio in AHI. Syphilis infection results in decreased gamma delta T-cell activation in AHI, but increased gamma delta T-cell activation in chronic HIV-1 infection (CHI). Moreover, patients with CHI had larger numbers of IL-17-producing gamma delta T cells than those with AHI, regardless of syphilis status. Thus, syphilis affected the gamma delta T-cell immune response differently in patients depending on the stages of HIV-1 disease. In addition, the percentage of IL-17-producing gamma delta T cells was positively correlated with the percentage of neutrophils. These results suggest that the gamma delta T-cell/ IL-17/neutrophil axis is involved in HIV-1 pathogenesis and disease progression. Taken together, our observations provide new insight into the roles of gamma delta T cells in immunopathogenesis of syphilis and HIV-1 coinfection, particularly during AHI, and our findings may be helpful for the prevention of syphilis and other sexually transmitted infections and highlight the great significance on the remedy of patients coinfected with HIV-1.