Role of CD14 in lung inflammation and infection

Anas, Adam A.; Poll, Tom van der; Vos, Alex F. de

doi:10.1186/cc8850

Cited by 67 publications

(38 citation statements)

References 53 publications

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“…The viscous circle of viral replication and inflammation is created and maintained by the “leaky gut” as suggested by Douek et al [28]. One should acknowledge that the sCD14 levels are also elevated in other infections (RSV, Dengue Virus, Mycobacteria) and inflammatory conditions [29], [30]. Thus, although analysis of sCD14 is important for the evaluation of MT in the setting of HIV-1 infected patients, it cannot be considered as a specific marker for MT alone.…”

Section: Discussionmentioning

confidence: 96%

Kinetics of Microbial Translocation Markers in Patients on Efavirenz or Lopinavir/r Based Antiretroviral Therapy

et al. 2013

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ObjectivesWe investigated whether there are differences in the effects on microbial translocation (MT) and enterocyte damage by different antiretroviral therapy (ART) regimens after 1.5 years and whether antibiotic use has impact on MT. In a randomized clinical trial (NCT01445223) on first line ART, patients started either lopinavir/r (LPV/r) (n = 34) or efavirenz (EFV) containing ART (n = 37). Lipopolysaccharide (LPS), sCD14, anti-flagellin antibodies and intestinal fatty acid binding protein (I-FABP) levels were determined in plasma at baseline (BL) and week 72 (w72).ResultsThe levels of LPS and sCD14 were reduced from BL to w72 (157.5 pg/ml vs. 140.0 pg/ml, p = 0.0003; 3.13 ug/ml vs. 2.85 ug/ml, p = 0.005, respectively). The levels of anti-flagellin antibodies had decreased at w72 (0.35 vs 0.31 [OD]; p<0.0004), although significantly only in the LPV/r arm. I-FABP levels increased at w72 (2.26 ng/ml vs 3.13 ng/ml; p<0.0001), although significantly in EFV treated patients only. Patients given antibiotics at BL had lower sCD14 levels at w72 as revealed by ANCOVA compared to those who did not receive (Δ = −0.47 µg/ml; p = 0.015).ConclusionsMarkers of MT and enterocyte damage are elevated in untreated HIV-1 infected patients. Long-term ART reduces the levels, except for I-FABP which role as a marker of MT is questionable in ART-experienced patients. Why the enterocyte damage seems to persist remains to be established. Also antibiotic usage may influence the kinetics of the markers of MT.Trial RegistrationClinicalTrials.gov NCT01445223

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Section: Discussionmentioning

confidence: 96%

Kinetics of Microbial Translocation Markers in Patients on Efavirenz or Lopinavir/r Based Antiretroviral Therapy

et al. 2013

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“…With this method, it was possible-depending on the initial applied bacterial dose-to detect the major cytokines TNF-a and Il-1b, which are elevated during sepsis or severe infection [21,22]. A further dynamic sign of the antibacterial capacity of differentiated EBs was a significant upregulation of the CD14 antigen, which mediates the recognition of LPS [23,24]. Another known key regulator of unspecific host defense and several bacterial killing processes is the activity of NOX2, which interestingly showed a significant upregulation during the coincubation of E. coli with EBs [14].…”

Section: Discussionmentioning

confidence: 99%

Antibacterial Capacity of Differentiated Murine Embryonic Stem Cells During Defined In Vitro Inflammatory Conditions

Finkensieper

Bekhite

Fischer

et al. 2013

Stem Cells and Development

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Embryonic stem (ES) cells are a powerful model for the development of cells responsible for the cellular immune response. Therefore, we analyzed the defense and phagocytic capacity of embryoid bodies (EBs) derived from ES cells using in the vitro inflammatory conditions caused by Escherichia coli. Further, we used this phagocytic activity to purify activated immune cells. Our data show that spontaneously differentiated 18-day-old EBs of the cell line CGR8 contained immune cells, which were positive for CD45, CD68, CD11b, F4/80, and CD19. Exposure of these EBs to E. coli with defined infection doses of bacterial colony-forming units (CFUs) led to a significant time-dependent reduction of CFUs, indicating the immune responses exerted by EBs. This was paralleled by an upregulation of inflammatory cytokines, that is, IL-1β and TNF-α. Western blot analysis of infected EBs indicated an upregulation of CD14 and cytochrome b-245 heavy chain (NOX2). Silencing of NOX2 significantly reduced the antibacterial capacity of EBs, which was partially explained by reduction of F4/80-positive cells. To identify, isolate, and further cultivate phagocytic active cells from differentiated EBs, a cocultivation assay of differentiated ES cells with green fluorescent protein (GFP)-labeled E. coli was established. Colocalization of GFP-labeled E. coli with cells positive for CD45, CD68, and F4/80 revealed time-dependent phagocytotic uptake, which was underlined by colocalization with the LysoTracker-Red(®) dye as well as preincubation with cytochalasin D. In conclusion, a primitive immune response with efficient phagocytosis was responsible for the antibacterial capacity of differentiated EBs.

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“…Even though sCD14 is one of the important markers for the evaluation of MT, it cannot be considered as a specific marker for MT because sCD14 levels are also elevated in other infections (RSV, dengue virus, mycobacteria) and inflammatory conditions. 48,49 …”

Section: Discussionmentioning

confidence: 99%

Immune Activation Is Associated With Increased Gut Microbial Translocation in Treatment-Naive, HIV-Infected Children in a Resource-Limited Setting

Pilakka-Kanthikeel

Arheart

Selvaraj

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Gut damage resulting in microbial translocation (MT) is considered a major cause of immune activation (IA) in HIV infection, but data in children are limited, particularly in the absence of antiretroviral therapy. Methods Sixty perinatally HIV-infected, antiretroviral therapy–naive children, aged 2–12 years, were evaluated for plasma levels of lipopolysaccharide, DNA sequences encoding bacterial ribosomal 16 second (16S) RNA (16S rDNA) and soluble CD14 concurrently with markers of CD4 and CD8 T-cell IA and immune exhaustion (IE), CD4 counts, and plasma viral load. At study entry, participants were classified into immune categories (ICs): IC1 (CD4% > 25), IC2 (CD4% 15–25), and IC3 (CD4% < 15). Age-matched HIV-uninfected children served as controls. Data were evaluated at study entry and at 12 months. Results Levels of MT, IA, and IE were increased in patients as compared with controls, were highest in patients in IC3 group, and did not change over 12 months. MT products lipopolysaccharide and 16S rDNA correlated with each other and each correlated with plasma viral load, soluble CD14, and T-cell IA and IE. There was a correlation of IA with IE. CD4 counts and percentage were inversely correlated with MT products and underlying CD4 activation. Conclusions In a natural history cohort of HIV-infected children not on therapy, MT was more pronounced in the most severely immunocompromised patients and was associated with IA. Strategies to reduce MT may help to reduce IA and prevent CD4 depletion.

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Role of CD14 in lung inflammation and infection

Cited by 67 publications

References 53 publications

Kinetics of Microbial Translocation Markers in Patients on Efavirenz or Lopinavir/r Based Antiretroviral Therapy

Kinetics of Microbial Translocation Markers in Patients on Efavirenz or Lopinavir/r Based Antiretroviral Therapy

Antibacterial Capacity of Differentiated Murine Embryonic Stem Cells During Defined In Vitro Inflammatory Conditions

Immune Activation Is Associated With Increased Gut Microbial Translocation in Treatment-Naive, HIV-Infected Children in a Resource-Limited Setting

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