Early Impairment of Gut Function and Gut Flora Supporting a Role for Alteration of Gastrointestinal Mucosa in Human Immunodeficiency Virus Pathogenesis

Gori, Andrea; Tincati, Camilla; Rizzardini, Giuliano; Torti, Carlo; Quirino, Tiziana; Haarman, Monique; Amor, Kaouther Ben; Schaik, Jacqueline van; Vriesema, Aldwin; Knol, Jan; Marchetti, Giulia; Welling, Gjalt W.; Clerici, Mario

doi:10.1128/jcm.01729-07

Cited by 198 publications

(180 citation statements)

References 17 publications

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“…Pathogenic SIV as well as HIV infection results in rapid and significant Th17 loss from the GALT which would be expected to have deleterious effects on the regulation of microbial translocation (Brenchley, Schacker et al, 2004;Raffatellu, Santos et al, 2008). Indeed, HIV infection is correlated with increases in microbial translocation and mucosal inflammation (Gori, Tincati et al, 2008). This is supported by studies showing that plasma LPS levels, considered as an indication of microbial translocation, in HIV infected individuals are remarkably higher than uninfected individuals (Jiang, Lederman et al, 2009;d'Ettorre, Paiardini et al, 2011).…”

Section: Th17 Cells and Hiv Infectionsupporting

confidence: 69%

Impact of HIV Infection and HAART Therapy on CD4 T Helper Cell Subset Expression and Function

Guzzo¹,

Mat²,

Zhang³

et al. 2011

HIV-Host Interactions

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Section: Th17 Cells and Hiv Infectionsupporting

confidence: 69%

Impact of HIV Infection and HAART Therapy on CD4 T Helper Cell Subset Expression and Function

Guzzo¹,

Mat²,

Zhang³

et al. 2011

HIV-Host Interactions

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“…Altered stool composition has also been reported, with increased levels of fecal calprotectin, which is secreted by recruited neutrophils in the intestinal lining and has been proposed to be a marker of intestinal inflammation (103). Taken together, these data demonstrate a substantial subversion of physiological gut microbiome and a correlation between pathogenic intestinal flora and gut inflammation in HIV disease (102). In a recent study, Ellis et al (64) explored the intriguing hypothesis that the gut microflora composition affects both local and systemic immunity, in analogy with what was described in several clinical settings (104,105).…”

Section: Characterization Of Stool Microbes and Translocating Flora Isupporting

confidence: 54%

“…Interestingly, Gori et al demonstrated that HIV-infected individuals in early stages of disease are characterized by an impaired fecal flora, with a predominance of opportunistic pathogens (Pseudomonas aeruginosa and Candida albicans) and low levels of protective bacteria (bifidobacteria and lactobacilli) compared with historical data on healthy HIV-uninfected persons (102). Altered stool composition has also been reported, with increased levels of fecal calprotectin, which is secreted by recruited neutrophils in the intestinal lining and has been proposed to be a marker of intestinal inflammation (103).…”

Section: Characterization Of Stool Microbes and Translocating Flora Imentioning

confidence: 99%

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

2013

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SUMMARYIn pathogenic simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infections, the translocation of microbial products from the gastrointestinal (GI) tract to portal and systemic circulation has been proposed as a major driver of the chronic immune activation that is associated with disease progression. Consistently, microbial translocation is not present in nonpathogenic SIV infections of natural host species.In vivostudies demonstrated that HIV/SIV-associated microbial translocation results from a series of immunopathological events occurring at the GI mucosa: (i) early and severe mucosal CD4+depletion, (ii) mucosal immune hyperactivation/persistent inflammation; (iii) damage to the integrity of the intestinal epithelium with enterocyte apoptosis and tight junction disruption; and (iv) subverted the gut microbiome, with a predominance of opportunistic bacteria. Directin situevidence of microbial translocation has been provided for SIV-infected rhesus macaques showing translocated microbial products in the intestinal lamina propria and distant sites. While the mechanisms by which microbial translocation causes immune activation remain controversial, a key pathogenic event appears to be innate immunity activation via Toll-like receptors and other pathogen recognition receptors. Accumulating clinical observations suggest that microbial translocation might affect HIV disease progression, response to therapy, and non-AIDS comorbidities. Given its detrimental effect on overall immunity, several interventions to prevent/block microbial translocation are currently under investigation as novel therapeutic agents for HIV/AIDS.

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“…LPS, which is a major structural component of the outer wall of Gram-negative bacteria and an effective CD14/TLR4 trigger, has been shown to be gradually increased in peripheral blood with the disease progression in HIV-1-infected subjects (19,(44)(45)(46)(47)(48). Because LY6E is upregulated during HIV-1 infection and plays a regulatory role in monocytes through modulating the expression of CD14, the innate immune responses to LPS stimulation in monocytes are likely to be attenuated via downregulating CD14/TLR4 pathway, as shown in our data ex vivo (Fig.…”

Section: Discussionmentioning

confidence: 99%

IFN-Stimulated Gene LY6E in Monocytes Regulates the CD14/TLR4 Pathway but Inadequately Restrains the Hyperactivation of Monocytes during Chronic HIV-1 Infection

Qiu

Zhu

et al. 2014

The Journal of Immunology

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Owing to ongoing recognition of pathogen-associated molecular patterns, immune activation and upregulation of IFN-stimulated genes (ISGs) are sustained in the chronically infected host. Albeit most ISGs are important effectors for containing viral replication, some might exert compensatory immune suppression to limit pathological dysfunctions, although the mechanisms are not fully understood. In this study, we report that the ISG lymphocyte Ag 6 complex, locus E (LY6E) is a negative immune regulator of monocytes. LY6E in monocytes negatively modulated CD14 expression and subsequently dampened the responsiveness to LPS stimulation in vitro. In the setting of chronic HIV infection, the upregulation of LY6E was correlated with reduced CD14 level on monocytes; however, the immunosuppressive effect of LY6E was not adequate to remedy the hyperresponsiveness of activated monocytes. Taken together, the regulatory LY6E pathway in monocytes represents one of negative feedback mechanisms that counterbalance monocyte activation, which might be caused by LPS translocation through the compromised gastrointestinal tract during persistent HIV-1 infection and may serve as a potential target for immune intervention.

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Early Impairment of Gut Function and Gut Flora Supporting a Role for Alteration of Gastrointestinal Mucosa in Human Immunodeficiency Virus Pathogenesis

Cited by 198 publications

References 17 publications

Impact of HIV Infection and HAART Therapy on CD4 T Helper Cell Subset Expression and Function

Impact of HIV Infection and HAART Therapy on CD4 T Helper Cell Subset Expression and Function

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

IFN-Stimulated Gene LY6E in Monocytes Regulates the CD14/TLR4 Pathway but Inadequately Restrains the Hyperactivation of Monocytes during Chronic HIV-1 Infection

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