Abstract
Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation.
Highlights
Eradication of HIV infection has not been achieved except under unique circumstances [1,2]
We evaluated the kinetics of Th17 depletion, microbial translocation and subsequent immune activation in early acute HIV infection and the effect of early initiated antiretroviral therapy (ART) on these events
We discovered that a collapse of Th17 cell number and function, accompanied by local and systemic immune activation, occurs already during acute HIV infection
Summary
Eradication of HIV infection has not been achieved except under unique circumstances [1,2]. Acute HIV infection (AHI), defined here as the period between detectable HIV RNA viremia and reactive IgG enzyme immunoassay (EIA) antibody to HIV proteins [6,7], is marked by peak viremia (.106 copies/mL), the rapid depletion of gastrointestinal CD4+T cells, followed by a deterioration of the mucosal epithelium and increased microbial translocation [8,9,10], which may not be restored despite prolonged ART [11,12] In this context, the importance of an IL-17-producing subpopulation of CD4+T cells (Th17 cells) has been emphasized. Despite the significant benefits of ART, immune reconstitution in the gut is often incomplete and immune activation may persist [28,29]
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