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Chipman, J. G.

Publications and source records attributed to Chipman, J. G..

2 recordsLinked to original sources

HIV lymphoid tissue fibrosis occurs in the earliest stages of acute HIV infection and is associated with macrophage-derived TGF-β

HIV infection is associated with lymphatic tissue damage caused by collagen deposition in the fibroblastic reticular cell network (FRCn) of the parafollicular T cell zone (TZ), which leads to impaired antigen presentation, T cell depletion, and reduced antibody formation. In treated chronic HIV infection, damage persists despite antiretroviral therapy (ART), but it is not known if very early initiation of ART could limit damage and preserve immune function. We studied participants in the Thai RV254 acute infection cohort and found significant collagen deposition in the FRCn even in the earliest Fiebig stage 1 acute infection. The amount of TZ collagen correlates with the frequency of TGF-{beta}+ macrophages which, in turn, correlates with the frequency of HIV RNA-producing cells. We conclude that immediate initiation of ART may have limited impact in preventing or reversing collagen accumulation in LNs.

microbiology↗

Ongoing lymphoid HIV production drives pyroptosis and GLP-1 counter-regulation in ART-suppressed infection

Despite effective antiretroviral therapy (ART), many people with HIV (PWH) exhibit persistent immune activation (IA) and suffer metabolic comorbidities. We investigated whether residual HIV production in lymphoid tissues drives IA. Among 20 ART-suppressed PWH, HIV RNA+ cells were detected in lymph nodes and correlated directly with markers of pyroptosis, assessed via cleaved gasdermin D positivity, but not with most plasma cytokines or IA markers. Notably, glucagon-like peptide 1 (GLP-1), an enteroendocrine hormone with anti-inflammatory roles, was upregulated in the ileum of PWH and correlated directly with systemic cytokines but inversely with lymph node pyroptosis. These findings suggest that chronic occult inflammation in people with successfully suppressed HIV infection is mediated by persistent virus production in lymph nodes leading to pyroptosis, which may trigger compensatory anti-inflammatory enteroendocrine activation that may dampen pyroptosis. Targeting pyroptosis or enhancing GLP-1 signaling represent potential therapeutic strategies for modulating IA and managing metabolic comorbidities in PWH. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/698696v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@af8909org.highwire.dtl.DTLVardef@4dbc95org.highwire.dtl.DTLVardef@197ff48org.highwire.dtl.DTLVardef@1f9051a_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗