Gut TLRs and IFN pathway mRNA expression and frequencies of CD4+ T Cell expressing CD38 or HLA-DR go in Parallel During HIV Immunopathogenesis

Luca Maddaloni; Ginevra Bugani; Letizia Santinelli; Alessandro Lazzaro; Federica Frasca; Matteo Fracella; Giancarlo Ceccarelli; Claudio M Mastroianni; Carolina Scagnolari; Gabriella d'Ettorre

doi:10.1016/j.imlet.2025.106973

Gut TLRs and IFN pathway mRNA expression and frequencies of CD4⁺ T Cell expressing CD38 or HLA-DR go in Parallel During HIV Immunopathogenesis

Immunol Lett. 2025 Jan 5:106973. doi: 10.1016/j.imlet.2025.106973. Online ahead of print.

Affiliations

¹ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy. Electronic address: [email protected].
² Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy. Electronic address: [email protected].
³ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy. Electronic address: [email protected].
⁴ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy. Electronic address: [email protected].
⁵ Virology Laboratory, Department of Molecular Medicine, Sapienza University of Rome, Italy. Electronic address: [email protected].
⁶ Virology Laboratory, Department of Molecular Medicine, Sapienza University of Rome, Italy. Electronic address: [email protected].
⁷ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy; Azienda Ospedaliero-Universitaria Policlinico Umberto I Rome, Italy.
⁸ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy. Electronic address: [email protected].
⁹ Virology Laboratory, Department of Molecular Medicine, Sapienza University of Rome, Italy. Electronic address: [email protected].
¹⁰ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy. Electronic address: [email protected].

PMID: 39765313
DOI: 10.1016/j.imlet.2025.106973

Abstract

Whereas much knowledge exists on the expression of IFN pathways in the blood of people living with HIV (PLWH), its role has only recently been appreciated in the gastrointestinal tract. Thus, the aim was to evaluate the gut mRNA expression levels of innate immune genes involved in the HIV-host interaction and their association with CD4⁺ T cell activation in long-term HAART-experienced PLWH. PLWH had increased TLR4, IFN-α2, IFN-α14, IFN-β and IFNAR1 mRNAs levels in LPLs, 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 frequencies of CD4⁺ T cells expressing CD38 or HLA-DR. These findings suggest a dysregulation in innate immunity, particularly of TLRs and IFN pathway in the gut of PLWH. Genes in these pathways also appear to be correlated with the levels of CD4⁺ T cells activation.

Keywords: CD4+ T lymphocytes; HAART; HIV; gut; innate immunity; type I interferon.