Persistent Microbial Translocation and Immune Activation in HIV‐1–Infected South Africans Receiving Combination Antiretroviral Therapy

Cassol, Edana; Malfeld, Susan; Mahasha, Phetole Walter; Merwe, Schalk van der; Cassol, Sharon; Seebregts, Christopher J.; Alfano, Massimo; Poli, Guido; Rossouw, Theresa M.

doi:10.1086/655229

Cited by 186 publications

(156 citation statements)

References 49 publications

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“…27,31,33 Our study results show that microbial translocation marker sCD14 was significantly elevated in the plasma from HIV-infected patients, consistent with previous studies. 45,46 Moreover, sCD14 showed significant correlation with HLA-DR 1 cd T cells.…”

Section: Chronic Immune Activation Depletes Memory Vd 2 CD T Cells Insupporting

confidence: 92%

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Distortion of memory Vδ2 γδ T cells contributes to immune dysfunction in chronic HIV infection

Jiao

et al. 2014

Cell Mol Immunol

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Section: Chronic Immune Activation Depletes Memory Vd 2 CD T Cells Insupporting

confidence: 92%

“…[31][32][33] LPS, a marker of microbial translocation, positively correlates with CD8 1 T-cell activation. 27 LBP is a serum glycoprotein that initiates an immune response after recognition of bacterial LPS in vivo.…”

Section: Microbial Translocation Contributes To Elevated Activation Omentioning

confidence: 99%

Distortion of memory Vδ2 γδ T cells contributes to immune dysfunction in chronic HIV infection

Jiao

et al. 2014

Cell Mol Immunol

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“…Analogously, Jiang et al showed that higher levels of DNA sequences encoding bacterial 16S rRNA genes are associated with greater T-cell activation and impaired CD4 ϩ T-cell restoration after ART (45). Similar data were also reported for a South African cohort, confirming persistently elevated LPS and sCD14 levels in INR despite virologically suppressive ART (62). While these findings provide important insights into the mechanisms determining the immunological response to ART, they still fail to formally prove that the level of microbial translocation is a key factor regulating CD4 ϩ T-cell reconstitution upon virologically suppressive ART.…”

Section: Clinical Implications Of Microbial Translocation In Hiv Disesupporting

confidence: 64%

“…Circulating levels of LPS have been consistently reported to decrease after the initiation of ART, even though they did not return to the levels observed for healthy HIV-uninfected individuals (33,39,45,62,65). Since persistent immune activation has long been implicated as a factor impairing the immunological response to ART (13,14), the question as to whether microbial translocation might affect immune recovery after ART has been investigated by different groups in the last few years.…”

Section: Clinical Implications Of Microbial Translocation In Hiv Disementioning

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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“…Activated CD14 + macrophages in necrotising enterocolitis produce nitric oxide (NO) that impairs endothelial repair [11,12]. We have shown that macrophages activation in HIV correlated with bacterial translocation and persistent immune activation [13].…”

Section: Introductionmentioning

confidence: 99%

Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function

Plessis

Vanheel

Janssen

et al. 2013

Journal of Hepatology

155

123

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Background & Aims: Bacterial infections commonly occur in decompensated cirrhosis resulting from bacterial translocation from the intestine. We studied the role of intestinal macrophages and the epithelial barrier in cirrhosis. Methods: Forty-four patients with NASH/ASH cirrhosis (decom-pensated n = 29, compensated n = 15) and nineteen controls undergoing endoscopy were recruited. Serum was obtained and LPS and LBP levels determined. Intestinal macrophages were characterized by flow cytometry, immunohistochemistry, and nitric oxide (NO) production measured in supernatant of cultured duodenal samples. Quantitative RT-PCR was performed on duo-denal biopsies assessing 84 inflammatory genes. Protein levels of cytokines/chemokines were assessed in serum and superna-tant. The duodenal wall was assessed by electron microscopy, tight junction protein expression determined by RT-PCR, immu-nohistochemistry, and Western blot and, functional analysis performed by transepithelial resistance measurement and per-meability studies. Results: Increased plasma LPS, LBP levels and higher numbers of duodenal CD33 + /CD14 + /Trem-1 + macrophages, synthesizing iNOS and secreting NO were present in decompensated cirrhosis. Upregulation of IL-8, CCL2, CCL13 at the transcriptional level, and increased IL-8, and IL-6 were detected in supernatant and serum in cirrhosis. IL-6 and IL-8 co-localised with iNOS + and CD68 + , but not with CD11c + cells. Electron microscopy demon-strated an intact epithelial barrier. Increased Claudin-2 was detected by Western blot and immunohistochemistry, while decreased transepithelial resistance and increased duodenal per-meability were detected in decompensated cirrhosis. Conclusions: Our study shows the presence of activated CD14 +-Trem-1 + iNOS + intestinal macrophages, releasing IL-6, NO, and increased intestinal permeability in patients with cirrhosis, sug-gesting that these cells may produce factors capable of enhancing permeability to bacterial products.

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Persistent Microbial Translocation and Immune Activation in HIV‐1–Infected South Africans Receiving Combination Antiretroviral Therapy

Abstract: Microbial translocation is a major force driving chronic inflammation in HIV-infected Africans receiving cART. Prevention of monocyte activation may be especially effective at enhancing therapeutic outcomes.

Cited by 186 publications

References 49 publications

Distortion of memory Vδ2 γδ T cells contributes to immune dysfunction in chronic HIV infection

Distortion of memory Vδ2 γδ T cells contributes to immune dysfunction in chronic HIV infection

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function

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