Different biological significance of sCD14 and LPS in HIV-infection: Importance of the immunovirology stage and association with HIV-disease progression markers

Romero-Sánchez, M. Concepción; González‐Serna, Alejandro; Pacheco, Yolanda M.; Ferrando‐Martínez, Sara; Machmach, Kawthar; García-García, María; Álvarez-Ríos, Ana Isabel; Vidal, Francisco; Leal, Manuel; Ruiz‐Mateos, Ezequiel

doi:10.1016/j.jinf.2012.06.008

Cited by 40 publications

(30 citation statements)

References 34 publications

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“…ϩϩ CD16 ϩ intermediate monocytes (10)(11)(12)46) and the plasma factors sCD14 (13,14,17,47) and sCD163 (15,16,40,48) as biomarkers of monocyte/macrophage activation and pathogenesis in SIV and HIV-1 disease. Therefore, we investigated the relationship between these variables and change in monocyte apoptosis with increasing viral load.…”

Section: Markers Of Innate Immune Activation Are Increased With Hivmentioning

confidence: 99%

Shift in Monocyte Apoptosis with Increasing Viral Load and Change in Apoptosis-Related ISG/Bcl2 Family Gene Expression in Chronically HIV-1-Infected Subjects

Patro

Pal

et al. 2015

J Virol

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Although monocytes and macrophages are targets of HIV-1-mediated immunopathology, the impact of high viremia on activation-induced monocyte apoptosis relative to monocyte and macrophage activation changes remains undetermined. In this study, we determined constitutive and oxidative stress-induced monocyte apoptosis in uninfected and HIV ؉ individuals across a spectrum of viral loads (n ‫؍‬ 35; range, 2,243 to 1,355,998 HIV-1 RNA copies/ml) and CD4 counts (range, 26 to 801 cells/mm 3 ). Both constitutive apoptosis and oxidative stress-induced apoptosis were positively associated with viral load and negatively associated with CD4, with an elevation in apoptosis occurring in patients with more than 40,000 (4.6 log) copies/ml. As expected, expression of Rb1 and interferon-stimulated genes (ISGs), plasma soluble CD163 (sCD163) IMPORTANCEThis study characterized differential monocyte activation, apoptosis, and apoptosis-related gene expression in low-versus highlevel viremic HIV-1 patients, suggesting a shift in apoptosis regulation that may be associated with disease state. Using single and multivariable analysis of monocyte activation parameters and gene expression, we supported the hypothesis that monocyte apoptosis in HIV disease is a reflection of viremia and activation state with contributions from gene expression changes within the ISG and Bcl2 gene families. Understanding monocyte apoptosis response may inform HIV immunopathogenesis, retention of infected macrophages, and monocyte turnover in low-or high-viral-load states.

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Section: Markers Of Innate Immune Activation Are Increased With Hivmentioning

confidence: 99%

Shift in Monocyte Apoptosis with Increasing Viral Load and Change in Apoptosis-Related ISG/Bcl2 Family Gene Expression in Chronically HIV-1-Infected Subjects

Patro

Pal

et al. 2015

J Virol

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“…Whether this is mediated by HIV severity remains unknown. 32 Second, the increased lower lung and, therefore, diff use emphysema in individuals with HIV infection points to potential vascular-related pathways consistent with the fi nding that systemic levels of sCD14 are associated with emphysema severity. Because blood fl ow tends to be greater in basal and dependent lung segments, 40 endothelial dysfunction in the setting of chronic HIV-related immune activation may lead to greater lower lung involvement and diff use emphysema.…”

Section: Discussionmentioning

confidence: 63%

“…[28][29][30][31] Elevated sCD14 levels may refl ect greater immune activation as a result of mucosal bacterial translocation despite ART. 16,20,32 High sCD14 is associated with increased mortality 20 and neurocognitive impairment 33 among individuals with HIV infection. Elevated sCD14 levels have also been identifi ed in BAL fl uid of smokers in the general population 34 and in patients with ARDS, 35 supporting a potential link with lung disease.…”

Section: Discussionmentioning

confidence: 99%

Increased Risk of Radiographic Emphysema in HIV Is Associated With Elevated Soluble CD14 and Nadir CD4

Attia

Akgün

Wongtrakool

et al. 2014

Chest

119

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“…This lack of association suggests that in this cohort, sCD14 does not specifically represent the construct of “microbial translocation,” but may represent non-specific monocyte activation, as discussed above. Although prior microbial translocation data have demonstrated that high levels of sCD14 in the plasma reflect LPS exposure[30], the two markers have not been reliably correlated in persons without significant immune suppression[90]; furthermore, in vivo work has shown IL-6 or IL-1β stimulation can induce sCD14 production comparable to that induced by LPS[91], suggesting inflammatory signaling independent of microbial translocation. Microbial translocation cannot be discounted as a factor in HIV-associated pulmonary disease based on this relatively small sample, but the contributions compared to other pathways appear to be limited.…”

Section: Discussionmentioning

confidence: 99%

Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

Fitzpatrick

Nouraie

Gingo

et al. 2016

Aids

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Objective Chronic obstructive pulmonary disease (COPD) is a common co-morbidity in HIV, with prevalence and severity of disease incompletely explained by risk factors such as smoking and age. Unique HIV-associated factors, including microbial translocation, monocyte activation, and endothelial dysfunction, have been described in other co-morbidities, but have not been investigated in relation to pulmonary abnormalities in HIV. This study assessed the relationship of these pathologic processes to pulmonary function in HIV-infected and uninfected individuals and determined if relationships were unique to HIV. Design Longitudinal observational study Methods 274 participants completed pulmonary function testing. Markers of inflammation (IL-6, IL-8, TNF-α), microbial translocation (lipopolysaccharide, sCD14), monocyte activation (sCD163, sCD14, and IL-2 receptor), and endothelial dysfunction (endothelin-1) were measured at baseline. Cross-sectional and longitudinal analyses were performed, adjusting for pertinent covariates. Results In HIV-infected individuals, higher IL-6 and endothelin-1 associated with worse FEV1 percent-predicted, and higher sCD163 associated with worse FEV1/FVC. IL-6, TNF-α, lipopolysaccharide, sCD163, IL-2 receptor, and endothelin-1 associated with diffusing impairment. sCD163 and endothelin-1 interacted with HIV status in relationship to pulmonary function. In HIV-infected individuals only, baseline endothelin-1 was associated with lower FEV1, and sCD163 and endothelin-1 were associated with lower diffusing capacity during follow-up. Conclusions Circulating markers of HIV-associated humoral abnormalities are associated with airflow obstruction and diffusing impairment, and baseline measures of monocyte activation and endothelial dysfunction associate with lower pulmonary function over time in HIV-infected persons. These findings suggest mechanisms of the disproportionate burden of COPD in HIV-infected persons.

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Different biological significance of sCD14 and LPS in HIV-infection: Importance of the immunovirology stage and association with HIV-disease progression markers

Cited by 40 publications

References 34 publications

Shift in Monocyte Apoptosis with Increasing Viral Load and Change in Apoptosis-Related ISG/Bcl2 Family Gene Expression in Chronically HIV-1-Infected Subjects

Shift in Monocyte Apoptosis with Increasing Viral Load and Change in Apoptosis-Related ISG/Bcl2 Family Gene Expression in Chronically HIV-1-Infected Subjects

Increased Risk of Radiographic Emphysema in HIV Is Associated With Elevated Soluble CD14 and Nadir CD4

Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

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