Journal
MUCOSAL IMMUNOLOGY
Volume 11, Issue 1, Pages 236-248Publisher
SPRINGERNATURE
DOI: 10.1038/mi.2017.44
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Funding
- Fundacao para a Ciencia e Tecnologia (FCT)
- Programa Operacional Ciencia e Inovacao [EXPL/DTP-PIC/0854/2013, PIC/IC/82712/2007]
- FundacaoCalouste Gulbenkian [P132532/2013]
- FCT scholarships
- Fundação para a Ciência e a Tecnologia [EXPL/DTP-PIC/0854/2013, PIC/IC/82712/2007] Funding Source: FCT
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The mechanisms that enable preservation of gut mucosal integrity during persistent viral replication and inherent inflammation remain unclear. Here, we investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally occurring form of attenuated HIV disease. We found viral replication in both sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating CD4+T-cells per mu l) despite their undetectable viremia, accompanied by interferon-gamma-producing CD8 T-cell expansion, irrespective of antiretroviral treatment. Nevertheless, there was no CD4 T-cell depletion, and Foxp3+ and IL-17-or IL-22-producing CD4 T-cell numbers were unaffected. Moreover, IL-22-producing innate lymphoid cells and IL-22-induced antimicrobial peptides and mucins were maintained. In agreement, the epithelium histology was preserved, including tight junction protein zonula occludens (ZO-1) levels. Furthermore, in vitro infection of colon epithelia with primary isolates revealed no HIV-2 impact on ZO-1 expression. Notably, sigmoid transcriptional levels of CCL20 and CCL28 were significantly increased, in direct correlation with GM-CSF, indicating a local response able to enhanceCD4T-cell recruitment. In conclusion, maintenance of mucosal integrity in HIV-2 infection was associated with T-cell recruitment responses, potentially counteracting CD4 T-cell depletion due to HIV-2 replication. These data have unique implications for the design of therapies targeting gut homeostasis in HIV-1 infection and other chronic inflammatory settings.
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