Gut TLRs and IFN pathways mRNA expression and frequencies of CD4+T cell expressing CD38 or HLA-DR go in parallel during HIV immunopathogenesis

Abstract

While much is known about the expression of interferon (IFN) pathways in the blood of people living with HIV (PLWH), their role in the intesinal tract has only recently been appreciated. The aim of this study was to evaluate gut mRNA expression levels of innate immune genes involved in the HIV-host interaction and their association with CD4⁺T cell immune activation in long-term HAART-experienced PLWH. PLWH had increased intestinal levels of TLR4, type I IFN (IFN-α2, IFN-α14, IFN-β) and IFNAR1 mRNAs, as well as increased frequencies of CD4⁺T lymphocytes expressing CD38 or HLA-DR compared to the healthy donors. Moreover, TLR4, TLR9, IRF3, IRF7 and IFN-α14 mRNA expression was positively correlated with the frequency of CD4⁺T cells expressing CD38 or HLA-DR. These findings suggest a dysregulation of innate immunity, particularly of the TLRs and IFN pathways in the gut of PLWH. Genes in these pathways also appear to correlate with the levels of CD4⁺T cell immune activation.

Keywords: CD4+ T lymphocytes; Gut; HIV; Innate immunity; T cell immune activation; TLR; type I interferon.