Human Immunodeficiency Virus-Related Microbial Translocation and Progression of Hepatitis C

Balagopal, Ashwin; Philp, Frances Hite; Astemborski, Jacquie; Block, Timothy M.; Mehta, Anand; Long, Ronald E.; Kirk, Gregory D.; Mehta, Shruti H.; Cox, Andrea L.; Thomas, David L.; Ray, Stuart C.

doi:10.1053/j.gastro.2008.03.022

Cited by 256 publications

(238 citation statements)

References 43 publications

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“…Balagopal et al demonstrated that in HIV-infected individuals, measures of microbial translocation are strongly associated with markers of hepatitis C virus (HCV)-related liver disease progression (e.g., cirrhosis) (123). Similarly, for 98 HIV/HCV coinfected patients on virologically suppressive ART, we reported increased sCD14 levels in subjects either harboring aggressive HCV genotypes (i.e., genotypes 1 to 4) or presenting with cirrhosis (129).…”

Section: Microbial Translocation In Liver Diseasesupporting

confidence: 66%

“…Indeed, LPS has been shown to accelerate liver fibrosis through TLR-4 signaling on Kupffer cells following membrane binding via LPS binding protein (LBP) and CD14 (121). These events lead to the generation of superoxide and the release of proinflammatory and profibrogenic cytokines such as TNF-␣, IL-1, IL-6, and IL-12, all of which induce liver damage (122,123). Consistent with these findings, microbial translocation has been shown to contribute to liver disease in several clinical settings, such as alcoholic liver disease (124,125) and other enteric processes (126)(127)(128).…”

Section: Microbial Translocation In Liver Diseasementioning

confidence: 99%

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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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Section: Microbial Translocation In Liver Diseasesupporting

confidence: 66%

Section: Microbial Translocation In Liver Diseasementioning

confidence: 99%

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

2013

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“…Whereas the hallmark of primary HIV infection is a substantial CD4 ϩ T cell loss at mucosal sites and elsewhere (20), chronic HIV infection is characterized by the inability of the immune system to control viral replication (22) as well as by a state of chronic immune activation. Mucosal translocation of microbial bioactive substances such as lipopolysaccharides (LPS) may be an important stimulus of this chronic immune activation (4,5,9,11,14,20,29,40,42,49). In fact, markers of chronic activation, such as CD38 on CD8 ϩ T cells, appear to be better suited to predicting clinical progression in HIV infection than HIV RNA levels and CD4 ϩ T cell counts (18,24,26,28,46).…”

mentioning

confidence: 99%

An Exploratory Trial of Cyclooxygenase Type 2 Inhibitor in HIV-1 Infection: Downregulated Immune Activation and Improved T Cell-Dependent Vaccine Responses

Pettersen

Torheim

Dahm

et al. 2011

J Virol

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Chronic HIV infection is characterized by chronic immune activation and dysfunctional T cells with elevated intracellular cyclic AMP (cAMP), which inhibits the T cell activation capability. cAMP may be induced by prostaglandin E 2 following lipopolysaccharide (LPS)-induced upregulation of cyclooxygenase type 2 (COX-2) in monocytes due to the elevated LPS levels in patients with chronic HIV infection. This hypothesis was tested using celecoxib, a COX-2 inhibitor, for 12 weeks in HIV-infected patients without antiretroviral treatment in a prospective, open, randomized exploratory trial. Thirty-one patients were randomized in the trial; 27 completed the study, including 13 patients on celecoxib. Celecoxib reduced chronic immune activation in terms of CD38 density on CD8 ؉ T cells (؊24%; P ‫؍‬ 0.04), IgA levels (P ‫؍‬ 0.04), and a combined score for inflammatory markers (P < 0.05). Celecoxib further reduced the inhibitory surface receptor programmed death 1 (PD-1) on CD8 ؉ T cells (P ‫؍‬ 0.01), including PD-1 on the HIV Gag-specific subset (P ‫؍‬ 0.02), enhanced the number of CD3 ؉ CD4 ؉ CD25 ؉ CD127 lo/؊ Treg or activated cells (P ‫؍‬ 0.02), and improved humoral memory recall responses to a T cell-dependent vaccine (P ‫؍‬ 0.04). HIV RNA (P ‫؍‬ 0.06) and D dimers (P ‫؍‬ 0.07) tended to increase in the controls, whereas interleukin-6 (IL-6) possibly decreased in the treatment arm (P ‫؍‬ 0.10). In conclusion, celecoxib downmodulated the immune activation related to clinical progression of chronic HIV infection and improved T cell-dependent functions in vivo.

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“…Persistent systemic exposure to bacterial antigens from MT triggers immune activation and inflammation in HIVinfected adults (25,26). MT is associated with T-cell activation, which predicts systemic inflammation, mortality, HIV progression, and progression of comorbidities such as cardiovascular disease (25,26,(29)(30)(31).…”

Section: Bacteria and The Gi Tractmentioning

confidence: 99%

Heart–Lung Interaction via Infection

Morris

2014

Annals ATS

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Lung and cardiovascular disease are increasingly recognized to occur in the same patient populations. Infections, either through stimulation of inflammation or through direct infection, can lead to end-organ damage and have been postulated as a potential link between lung and cardiovascular diseases. Mechanisms by which infections may link lung and cardiac diseases include effects of systemic infections, microbial translocation of pathogens from the gastrointestinal tract or other sites, damaging effects of metabolic products, or influences of smoking on the microbiome.Other mechanisms, such as alterations in the local microbiome, environmental exposures, or immune regulation by microbial communities, may be important. These relationships are likely quite complex, with multiple routes between infection and disease possible. A better understanding of the links of infection to lung and heart disease can improve our understanding of the pathogenesis of these disorders and uncover novel therapeutic approaches.Keywords: microbial translocation; metabolomics; pulmonary function; cardiovascular; HIV Correspondence and requests for reprints should be addressed to Alison Morris, M.D., M.S.,

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Human Immunodeficiency Virus-Related Microbial Translocation and Progression of Hepatitis C

Cited by 256 publications

References 43 publications

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

An Exploratory Trial of Cyclooxygenase Type 2 Inhibitor in HIV-1 Infection: Downregulated Immune Activation and Improved T Cell-Dependent Vaccine Responses

Heart–Lung Interaction via Infection

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