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

Abstract

A rapidly escalating outbreak of syphilis infection has been affected men who have sex with men, particularly those with HIV-1 infection. γδ T cells are unconventional immune cells with two main subsets, Vδ1 T cells and Vδ2 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 γδ 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 γδ T-cell phenotype and function was performed by flow cytometry. We found syphilis coinfection could reverse the imbalance of Vδ1/Vδ2 ratio in AHI. Syphilis infection results in decreased γδ T-cell activation in AHI, but increased γδ T-cell activation in chronic HIV-1 infection (CHI). Moreover, patients with CHI had larger numbers of IL-17-producing γδ T cells than those with AHI, regardless of syphilis status. Thus, syphilis affected the γδ T-cell immune response differently in patients depending on the stages of HIV-1 disease. In addition, the percentage of IL-17-producing γδ T cells was positively correlated with the percentage of neutrophils. These results suggest that the γδ 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 γδ 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.

Early HIV infection is associated with reduced proportions of gamma delta T subsets as well as high creatinine and urea levels

“…A subset of γδ T cells have been shown to serve as reservoir for HIV infection . Finding in this study that IL‐17 levels were higher among CHIV persons compared to EHIV is similar to reports from previous studies . IL‐17 production has previously been largely attributed to γδ, DNT and neutrophils.…”

“…IL‐17 production has previously been largely attributed to γδ, DNT and neutrophils. This IL‐17/neutrophil/ γδ T cell production axis has been shown to be critical to HIV‐1 disease progression . Data from this study showed that high HIV‐1 RNA viral load as well as urea levels may impact negatively on the IL‐17/neutrophil/ γδ T cells axis thereby limiting their activation during the early stages of infection.…”

γδ T‐cell responses during HIV infection and antiretroviral therapy

“…The destructive impact of HIV infection on Vd2 T cells stands in direct contrast to the observed expansion of peripheral Vd1 T cells, 32,[36][37][38] which occurs rapidly during acute infection (and prior to HIV seroconversion 38 ). Several studies have confirmed that the relative enrichment of Vd1 cells as a proportion of the total cd T-cell population is also reflected as an increase in absolute Vd1 33,[38][39][40][41][42][43][44][45][46][47] ) T-cell count in the periphery. Similar to Vd2 cells, Vd1 cells are significantly more activated in HIV-infected subjects compared with controls.…”

“…10 However, they have been observed to expand in the blood in patients with cytomegalovirus infection, CD4 T-cell deficiency and B-cell leukaemia. 29 Multiple reports have since described an inversion of the typical Vd2:Vd1 T-cell ratio in the peripheral blood of HIV-infected/AIDS patients, [30][31][32][33] which was quickly determined to represent an increase in Vd1 T-cell frequency 30,[32][33][34][35][36][37][38][39][40][41][42][43][44] and a depletion of Vd2Vc9 T cells. In 2017, an estimated 36.9 million people were currently infected with the virus of which 1.8 million were children under the age of 15.…”

“…28 While HIV is well known to impact the function and distribution of conventional T-cell subsets, the impact of the disease on cd T-cell subsets has been an ongoing subject of research since the late 1980s. 29 Multiple reports have since described an inversion of the typical Vd2:Vd1 T-cell ratio in the peripheral blood of HIV-infected/AIDS patients, [30][31][32][33] which was quickly determined to represent an increase in Vd1 T-cell frequency 30,[32][33][34][35][36][37][38][39][40][41][42][43][44] and a depletion of Vd2Vc9 T cells. [31][32][33]35,38,[41][42][43][44][45][46][47][48] Subsequent investigations have focused on the mechanisms behind this expansion/depletion, as well as the relationship of cd T subsets to HIV disease progression.…”