The Th17/Treg Ratio, IL-1RA and sCD14 Levels in Primary HIV Infection Predict the T-cell Activation Set Point in the Absence of Systemic Microbial Translocation

Abstract

Impairment of the intestinal barrier and subsequent microbial translocation (MT) may be involved in chronic immune activation, which plays a central role in HIV pathogenesis. Th17 cells are critical to prevent MT. The aim of the study was to investigate, in patients with primary HIV infection (PHI), the early relationship between the Th17/Treg ratio, monocyte activation and MT and their impact on the T-cell activation set point, which is known to predict disease progression. 27 patients with early PHI were included in a prospective longitudinal study and followed-up for 6 months. At baseline, the Th17/Treg ratio strongly negatively correlated with the proportion of activated CD8 T cells expressing CD38/HLA-DR or Ki-67. Also, the Th17/Treg ratio was negatively related to viral load and plasma levels of sCD14 and IL-1RA, two markers of monocyte activation. In untreated patients, the Th17/Treg ratio at baseline negatively correlated with CD8 T-cell activation at month 6 defining the T-cell activation set point (% HLA-DR+CD38+ and %Ki-67+). Soluble CD14 and IL-1RA plasma levels also predicted the T-cell activation set point. Levels of I-FABP, a marker of mucosal damages, were similar to healthy controls at baseline but increased at month 6. No decrease in anti-endotoxin core antibody (EndoCAb) and no peptidoglycan were detected during PHI. In addition, 16S rDNA was only detected at low levels in 2 out 27 patients at baseline and in one additional patient at M6. Altogether, data support the hypothesis that T-cell and monocyte activation in PHI are not primarily driven by systemic MT but rather by viral replication. Moreover, the “innate immune set point” defined by the early levels of sCD14 and IL-1RA might be powerful early surrogate markers for disease progression and should be considered for use in clinical practice.

Preferential loss of gut-homing α4β7 CD4+ T cells and their circulating functional subsets in acute HIV-1 infection

“…16,33,34 Altered gut-homing Treg:Th17 and Th1:Treg ratios were documented during chronic HIV-1 infection despite ART. 25 Abnormal ratios of Th1:Treg and Treg:Th17 were also demonstrated in AHIs (Figure 6b and 6c).…”

Higher levels of circulating monocyte–platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection

“…They have been reported to be upregulated in HIV infection and can act as predictive markers of HIV disease progression. [1][2][3][4][5][6] Increased coagulation biomarkers, such as Ddimer and/or thrombin-antithrombin complex, were also found to be correlated with sCD14 in pathogenic simian immunodeficiency virus infection. 41 In addition, we found that increased plasma levels of sCD14 and sCD163 were positively correlated with HIV-1 viremia, but were negatively correlated with the CD4 counts.…”

“…As markers of immune activation, the plasma sCD14 and sCD163 levels are elevated during HIV-1 infection and are useful in predicting the activation status of the monocyte response, HIV activity and pathogenesis. [1][2][3][4][5][6] Toll-like receptors (TLRs) are abundantly expressed on monocytes and are involved in innate monocyte responses. Many studies suggested that TLR responses contribute to the disease progression and clinical outcomes of viral infections, including HIV infections.…”

From Wasting to Obesity: The Contribution of Nutritional Status to Immune Activation in HIV Infection

“…However, the effect of GHRH on innate and cellular immune activation is still unclear. attributed to microbial translocation does not correspond entirely to markers of mucosal integrity or damage [15,32]. Despite the initiation of ART and plasma viral suppression, defects in junctional complex expression, the presence of bacterial products in the lamina propria, and reduced interleukin 17 (IL-17)-and (IL-22)-producing cells persist in treated HIV infection [28,33], and even the early initiation of ART shortly after infection does not fully normalize gastrointestinal mucosal dysfunction markers [34].…”