Gut Innate Immunity and HIV Pathogenesis

Dillon, Stephanie M.; Wilson, Cara C.

doi:10.1007/s11904-021-00544-3

Cited by 7 publications

(9 citation statements)

References 99 publications

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“…The GALT is organized into Peyer's patches in the small intestine, important for immune surveillance and the facilitating of immune responses in the mucosa (120). Innate immune cells like innate lymphoid cells (ILCs), macrophages and myeloid and plasmacytoid dendritic cells (mDC; pDC) provide protection against pathogens, drive adaptive immune responses and mediate intestinal homeostasis, and reside in the intra-epithelial layer and into the deeper lamina propria (121).…”

Section: An Overview Of Gut Mucosal Immunologymentioning

confidence: 99%

Probiotics to manage inflammation in HIV infection

Reikvam

Meyer‐Myklestad

Trøseid

et al. 2020

Current Opinion in Infectious Diseases

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Section: An Overview Of Gut Mucosal Immunologymentioning

confidence: 99%

Probiotics to manage inflammation in HIV infection

Reikvam

Meyer‐Myklestad

Trøseid

et al. 2020

Current Opinion in Infectious Diseases

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“…In this study, we leverage modulations in ERE activity at the RNA level in the GI tract of untreated PLWH with frequencies of immune cell populations that are likely critical players in driving HIV-1 gut pathogenesis 11 . As the derepression of EREs may possess immunomodulatory roles in human diseases 42,61 , our results suggest further investigation into their activity in HIV-1 pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Endogenous Retroelement Expression in the Gut Microenvironment of People Living with HIV-1

Dopkins,

Fei,

Michael

et al. 2023

Preprint

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SummaryBackgroundEndogenous retroelements (EREs), including human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs), comprise almost half of the human genome. HIV-1 infects a target cell already possessing ancient retroviral genetic material, and exogenous HIV-1 infection modulates the expression of cell associated EREs. Following initial HIV-1 infection, there is a rapid destruction of CD4+ cells in the gut associated lymphoid tissue (GALT). Our previous studies of the interferome in the gut suggest potential mechanisms regarding how IFNb may drive HIV-1 gut pathogenesis. As ERE activity is suggested to partake in type 1 immune responses and is incredibly sensitive to viral infections, we sought to elucidate underlying interactions between ERE expression and GALT dynamics in PLWH.MethodsERE expression profiles from bulk RNA sequencing of colon biopsies and PBMC were compared between a cohort of PLWH prior to or within 7 days of initiating antiretroviral therapy (ART) (n=19) and uninfected controls (n=13). Individual EREs were then compared with the profiling of uninfected gut CD4+ T cells activated with type 1 interferons (IFN-Is) (n=3) to elucidate potential mechanisms for their induction in PLWH.Findings59 EREs were differentially expressed in the colon of PLWH when compared to uninfected controls (Wald’s Test with Benjamin-Hochberg correction: padj < 0.05 and FC ≤ −1 or ≥ 1). Of these 59, 12 EREs were downregulated in PLWH and 47 were upregulated. Colonic expression of the ERE loci LTR19_12p13.31 and L1FLnI_1q23.1s showed significant correlations with CD8+ T Cells and dendritic cell subset frequencies in the GI tract (Spearman’s Correlation: p value < 0.05). Furthermore L1FLnI_1q23.1s showed a significant upregulation in the blood of PLWH when compared to uninfected controls (T test: p <0.05) suggesting a common mechanism of differential ERE expression in PBMC and GALT.InterpretationERE activity has been largely understudied in genomic characterizations of human pathologies. We show that the activity of certain EREs in the GI tract of PLWH is deregulated, supporting our hypotheses that their underlying activity could function as (bio)markers and potential mediators of pathogenesis in HIV-1 reservoirs.FundingNCI CA260691 (DFN) and NIAID UM1AI164559 (DFN).

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“…In contrast, monocytes/macrophages from rhesus monkeys were enriched for genes involved in antiviral immunity rather than wound healing. Likewise, in people with untreated HIV infection, there is an enrichment in proinflammatory macrophages in the gut 45 and evidence suggests that their inflammatory phenotype is a contributing factor to barrier dysfunction during chronic infection 46 . Identification of the mechanisms underlying these phenomena will require further studies involving various approaches, including immunologic, cell biologic, physiologic, and multiomic analyses.…”

Section: Macrophages In Hiv Pathogenesis and Comorbidities/coinfectio...mentioning

confidence: 99%

Role of macrophages in HIV pathogenesis and cure: NIH perspectives

Joseph

Daley

Lawrence

et al. 2022

Journal of Leukocyte Biology

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Macrophages play a significant role in HIV infection and contribute to pathogenesis of comorbidities as well as establishment of the viral reservoir in people living with HIV. While CD4+ T cells are considered the main targets of HIV infection, infected macrophages resist the cytopathic effects of infection, contributing to the persistent HIV reservoir. Furthermore, activated macrophages drive inflammation and contribute to the development of comorbidities, including HIV‐associated CNS dysfunction. Better understanding the role of macrophages in HIV infection, persistence, and comorbidities can lead to development of innovative therapeutic strategies to address HIV‐related outcomes in people living with HIV. In October 2021, the National Institute of Mental Health and the Ragon Institute of MGH, MIT, and Harvard conducted a virtual meeting on role of macrophages in HIV infection, pathogenesis, and cure. This review article captures the key highlights from this meeting and provides an overview of interests and activities of various NIH institutes involved in supporting research on macrophages and HIV.

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Gut Innate Immunity and HIV Pathogenesis

Cited by 7 publications

References 99 publications

Probiotics to manage inflammation in HIV infection

Probiotics to manage inflammation in HIV infection

Endogenous Retroelement Expression in the Gut Microenvironment of People Living with HIV-1

Role of macrophages in HIV pathogenesis and cure: NIH perspectives

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