Soluble CD14 and CD83 from Human Neonatal Antigen-Presenting Cells Are Inducible by Commensal Bacteria and Suppress Allergen-Induced Human Neonatal Th2 Differentiation

Department of Rheumatology and Inflammation Research, Göteborg University, Guldhedsgatan 10, 413 46 Göteborg, Sweden.
Infection and Immunity (Impact Factor: 3.73). 09/2007; 75(8):4097-104. DOI: 10.1128/IAI.01744-06
Source: PubMed


CD14 is expressed on the cell surface of various antigen-presenting cells, and CD83 is a maturation marker for dendritic cells
(DC). CD14 and CD83 are also present as soluble proteins, and both have immunoregulatory functions. We examined whether neonatal
cord blood monocytes or DC released soluble CD14 (sCD14) or sCD83 when exposed to the commensal intestinal bacteria Clostridium perfringens, Staphylococcus aureus, Lactobacillus rhamnosus, Escherichia coli, and Bacteroides fragilis. We found that the gram-positive bacteria C. perfringens and S. aureus, but not gram-negative bacteria, induced the release of sCD14 from monocytes. DC, on the other hand, released sCD14 in response
to both gram-positive and gram-negative bacteria. Moreover, the expression of the virulence factor staphylococcal protein
A seemed to be important for S. aureus-induced sCD14 production from both monocytes and DC. Soluble CD83 was released from DC, but not from monocytes, when exposed
to both gram-positive and gram-negative bacteria. Finally, to investigate whether sCD14 or sCD83 could modulate neonatal allergen-induced
T-cell differentiation, DC were exposed to birch allergen alone or in the presence of sCD14 or sCD83 and then cocultured with
autologous T cells. We demonstrate that sCD14 and sCD83 inhibited the birch allergen-induced Th2 differentiation by suppressing
interleukin 13 production. Together, these results suggest that the commensal intestinal flora may be an important stimulus
for the developing immune system by inducing the immunoregulatory proteins sCD14 and sCD83, which may be involved in preventing
T-cell sensitization to allergens in infants.

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    • "Alternatively, soluble CD14 may act as a suppressor of IL-13 expression in neurons. This theory is supported by a previous study suggesting suppression of IL-13 production from human dendritic cells by soluble CD14 molecule [11]. In the thalamus of CD14 À/À mice at 75 dpi, IL-13 expression appeared to be concurrent with deposition of PrP Sc . "
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    ABSTRACT: CD14 deficient (CD14−/−) mice survived longer than wild-type (WT) C57BL/6J mice when inoculated with prions intracerebrally, accompanied by increased expression of anti-inflammatory cytokine IL-10 by microglia in the early stage of infection. To assess the immune regulatory effects of CD14 in detail, we compared the gene expression of pro- and anti-inflammatory cytokines in the brains of WT and CD14−/− mice infected with the Chandler strain. Gene expression of the anti-inflammatory cytokine IL-13 in prion-infected CD14−/− mice was temporarily upregulated at 75 dpi, whereas IL-13 gene expression was not upregulated in prion-infected WT mice. Immunofluorescence staining showed that IL-13 was mainly expressed in neurons of the thalamus at 75 dpi. These results suggest that CD14 can suppress IL-13 expression in neurons during the early stage of prion infection.
    Preview · Article · Oct 2014 · Biochemical and Biophysical Research Communications
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    • "The soluble form of CD14, that lacks the glycosylphosphatidyl inositol tail, was abundant in serum [13] as well as in urine [7]. A few studies reported that the serum level of sCD14 was higher in patients with cancer than in patients with benign disease or healthy people [14,15,16], and therefore sCD14 has been considered to possibly play a part in immune tolerance [17,18] and in cancer development [16]. Here, we for the first time demonstrated that the breast cancer patients with a lower serum sCD14 level were at significantly higher risk of recurrence than those with higher serum sCD14 level. "
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    ABSTRACT: In clinical practice, breast cancers with lymph node positive, ER/PR-negative and overexpressed human epidermal growth factor receptor 2 (LN+ER/PR-Her2+) have high risk of recurrence, but the effective biomarkers of prognostic for this type tumor are still lacking. Since breast cancers with LN+ER/PR-Her2+ is at higher risk of recurrence than those with LN-ER/PR+Her2-. The differential proteins between those two groups could be related to the risk of recurrence. Herein, we report that serum soluble CD14 (sCD14) was revealed as the stable differential protein between LN+ER/PR-Her2+ (n=50) and LN-ER/PR+Her2- (n=50) breast cancer patients by proteomics analysis. To validate sCD14 as a biomarker for predicting recurrence of breast cancer, 90 breast cancer patients with LN+ER/PR-Her2+ and 93 patients with LN-ER/PR+Her2- were recruited. The patients with higher level of serum sCD14 at primary surgery showed to be at significantly lower risk of relapse in 3 years follow-up than those with lower level of serum sCD14 at primary surgery. The levels of serum sCD14 at primary surgery were significantly correlated to the risk of 3-year recurrence of LN+ER/PR-Her2+ breast cancer and the corresponding AUC of the ROC curve was 0.833 (95% CI, and 0.742 to 0.920). Therefore, we surmise that serum sCD14 could be a potential biomarker for predicting the prognosis of breast invasive ductal carcinoma with LN+ER/PR-Her2+.
    Full-text · Article · Sep 2013 · PLoS ONE
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    ABSTRACT: Soluble CD14 (sCD14) is a part of innate immunity that has been implicated in many diseases, including allergic diseases. However, many influencing factors and confounders, including gender-gene-environment interactions, may complicate interpretations of the observed associations to allergic diseases. In this paper, we review current literature describing the functions of sCD14 and its associations with common (recurrent) infections and with allergic diseases. Because sCD14 is involved with immunologic responses to infections, and exposure to microbial compounds is debated as a protective or a trigger factor for allergy development, these factors-which include genotypes, gender, age, microbial agents (from the environment and infection), and tobacco smoke-cannot be assessed independently. We conclude that confounding effects are important and must be considered to understand the role of sCD14 in allergic development.
    No preview · Article · Dec 2007 · Current Allergy and Asthma Reports
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