Gangliosides Act as Co-receptors for Salmonella enteritidis FliC and Promote FliC Induction of Human β-Defensin-2 Expression in Caco-2 Cells

Self Cite

320

225

The intestinal epithelium serves as a barrier to the intestinal flora. In response to pathogens, intestinal epithelial cells (IEC) secrete proinflammatory cytokines. To aid in defense against bacteria, IEC also secrete antimicrobial peptides, termed defensins. The aim of our studies was to understand the role of TLR signaling in regulation of β-defensin expression by IEC. The effect of LPS and peptidoglycan on β-defensin-2 expression was examined in IEC lines constitutively or transgenically expressing TLRs. Regulation of β-defensin-2 was assessed using promoter-reporter constructs of the human β-defensin-2 gene. LPS and peptidoglycan stimulated β-defensin-2 promoter activation in a TLR4- and TLR2-dependent manner, respectively. A mutation in the NF-κB or AP-1 site within the β-defensin-2 promoter abrogated this response. In addition, inhibition of Jun kinase prevents up-regulation of β-defensin-2 protein expression in response to LPS. IEC respond to pathogen-associated molecular patterns with expression of the antimicrobial peptide β-defensin-2. This mechanism may protect the intestinal epithelium from pathogen invasion and from potential invaders among the commensal flora.

Section: Discussionsupporting

confidence: 53%

Section: Expression Vectors and Cdna Constructsmentioning

confidence: 99%

β-Defensin-2 Expression Is Regulated by TLR Signaling in Intestinal Epithelial Cells

Vora¹,

Youdim²,

Thomas³

et al. 2004

Self Cite

320

225

“…ND ϩ RNA (99) expression of ␤-defensin-2 in intestinal epithelial cells (34,35). We have recently demonstrated that TLR4-and TLR2-dependent pathways can stimulate ␤-defensin-2 expression by intestinal epithelial cells (36).…”

Section: Secretion Of Anti-microbial Peptidesmentioning

confidence: 99%

TLR Signaling in the Gut in Health and Disease

Abreu

Fukata

Arditi

2005

533

382

The human intestine has evolved in the presence of diverse enteric microflora. TLRs convert the recognition of pathogen-associated molecules in the gut into signals for anti-microbial peptide expression, barrier fortification, and proliferation of epithelial cells. Healing of injured intestinal epithelium and clearance of intramucosal bacteria require the presence of intact TLR signaling. Nucleotide oligomerization domain (Nod)1 and Nod2 are additional pattern recognition receptors that are required for defense against invasive enteric pathogens. Through spatial and functional localization of TLR and Nod molecules, the normal gut maintains a state of controlled inflammation. By contrast, patients with inflammatory bowel disease demonstrate inflammation in response to the normal flora. A subset of these patients carry polymorphisms in TLR and CARD15/NOD2 genes. A better understanding of the delicate regulation of TLR and Nod molecules in the gut may lead to improved treatment for enteric infections and idiopathic inflammatory bowel diseases.

“…Furthermore, flagellin plays a role in triggering adaptive immune responses by stimulating chemokine secretion and migration and maturation of dendritic cells (32,33), and by modulating T cell activation in vivo (34). Flagellin is the ligand of TLR-5 (35,36), although additional receptors may modulate signaling (37,38). By contrast, alginate signals through TLR-2 and TLR-4 to induce cytokine expression in monocytes and macrophages (39), but the molecular mechanisms mediating the effects of alginate on epithelial cells, which constitute a first line of defense against pathogens in the airways, are unknown.…”

mentioning

confidence: 99%

Pseudomonas aeruginosa Flagellin and Alginate Elicit Very Distinct Gene Expression Patterns in Airway Epithelial Cells: Implications for Cystic Fibrosis Disease

Cobb

Mychaleckyj

Wozniak

et al. 2004

Infection with the opportunistic pathogen Pseudomonas aeruginosa remains a major health concern. Two P. aeruginosa phenotypes relevant in human disease include motility and mucoidy. Motility is characterized by the presence of flagella and is essential in the establishment of acute infections, while mucoidy, defined by the production of the exopolysaccharide alginate, is critical in the development of chronic infections, such as the infections seen in cystic fibrosis patients. Indeed, chronic infection of the lung by mucoid P. aeruginosa is a major cause of morbidity and mortality in cystic fibrosis patients. We have used Calu-3 human airway epithelial cells to investigate global responses to infection with motile and mucoid P. aeruginosa. The response of airway epithelial cells to exposure to P. aeruginosa motile strains is characterized by a specific increase in gene expression in pathways controlling inflammation and host defense. By contrast, the response of airway epithelia to the stimuli presented by mucoid P. aeruginosa is not proinflammatory and, hence, may not be conducive to the effective elimination of the pathogen. The pattern of gene expression directed by flagellin, but not alginate, includes innate host defense genes, proinflammatory cytokines, and chemokines. By contrast, infection with alginate-producing P. aeruginosa results in an overall attenuation of host responses and an antiapoptotic effect.