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. 2024 Apr 1;38(5):623-632.
doi: 10.1097/QAD.0000000000003799. Epub 2023 Dec 4.

Primary HIV infection features colonic damage and neutrophil inflammation yet containment of microbial translocation

Camilla Tincati  1 , Valeria Bono  1 , Elvira Stefania Cannizzo  1 , Delfina Tosi  2 , Federica Savi  2 , Camilla Falcinella  1 , Anna Casabianca  3 , Chiara Orlandi  3 , Carmelo Luigiano  4 , Matteo Augello  1 , Stefano Rusconi  5 , Antonio Muscatello  6 , Alessandra Bandera  6 , Andrea Calcagno  7 , Andrea Gori  8 , Silvia Nozza  9 , Giulia Marchetti  1 ; on behalf of the Italian Network of ACuTe HIV InfectiON (INACTION)
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Primary HIV infection features colonic damage and neutrophil inflammation yet containment of microbial translocation

Camilla Tincati et al. AIDS. .

Abstract

Introduction: Impairment of the gastrointestinal barrier leads to microbial translocation and peripheral immune activation, which are linked to disease progression. Data in the setting of primary HIV/SIV infection suggest that gut barrier damage is one of the first events of the pathogenic cascade, preceding mucosal immune dysfunction and microbial translocation. We assessed gut structure and immunity as well as microbial translocation in acutely and chronically-infected, combination antiretroviral therapy (cART)-naive individuals.

Methods: Fifteen people with primary HIV infection (P-HIV) and 13 with chronic HIV infection (C-HIV) c-ART-naive participants were cross-sectionally studied. Gut biopsies were analysed in terms of gut reservoirs (total, integrated and unintegrated HIV DNA); tight junction proteins (E-cadherin, Zonula Occludens-1), CD4 + expression, neutrophil myeloperoxidase (histochemical staining); collagen deposition (Masson staining). Flow cytometry was used to assess γδ T-cell frequency (CD3 + panγδ+Vδ1+/Vδ2+). In plasma, we measured microbial translocation (LPS, sCD14, EndoCAb) and gut barrier function (I-FABP) markers (ELISA).

Results: P-HIV displayed significantly higher tissue HIV DNA, yet neutrophil infiltration and collagen deposition in the gut were similar in the two groups. In contrast, microbial translocation markers were significantly lower in P-HIV compared with C-HIV. A trend to higher mucosal E-cadherin, and gut γδ T-cells was also observed in P-HIV.

Conclusion: Early HIV infection features higher HIV DNA in the gut, yet comparable mucosal alterations to those observed in chronic infection. In contrast, microbial translocation is contained in primary HIV infection, likely because of a partial preservation of E-cadherin and mucosal immune subsets, namely γδ T-cells.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Fig. 1
Fig. 1
HIV DNA quantification in gut biopsies.
Fig. 2
Fig. 2
Collagen deposition, T-cell counts and neutrophil infiltration in gut biopsies.
Fig. 3
Fig. 3
Tight junction protein expression in colon tissue of people with primary HIV and chronic HIV.
Fig. 4
Fig. 4
Markers of microbial translocation and intestinal damage in plasma.
See this image and copyright information in PMC

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