Airway epithelial cell signaling in response to bacterial pathogens

Gómez, M. A.; Prince, Alice

doi:10.1002/ppul.20735

Cited by 64 publications

(57 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years, a variety of in vitro studies have shown that various microbes are capable of activating epithelial cells in a TLR-dependent manner (1,9). Despite the multitude of studies dealing with bacterium-host interaction in vitro, little is known about the function of epithelial TLRs during bacterial colonization of the upper respiratory tract in vivo.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Early Bacterial Colonization Induces Toll-Like Receptor-Dependent Transforming Growth Factor β Signaling in the Epithelium

Beißwenger¹,

Лысенко²,

Weiser

2009

Infect Immun

View full text Add to dashboard Cite

Colonization of the upper respiratory tract is an initial step that may lead to disease for many pathogens. To prevent compromise of the epithelial barrier, the host must monitor and tightly control bacterial levels on the mucosa. Here we show that innate immune functions of respiratory epithelial cells control colonization by Streptococcus pneumoniae and Haemophilus influenzae in a Toll-like receptor (TLR)-dependent manner. Activation of inflammatory pathways, including mitogen-activated protein kinase signaling, in respiratory epithelial cells was accompanied by the induction of the transforming growth factor ␤ signaling cascade during early colonization. Thus, colonization resulted in upregulation of factors involved in a proinflammatory response (e.g., interleukin-6) as well as factors known to modulate the epithelial barrier (e.g., Snail-1). These in vivo data provided a link between inflammation control and maintenance of the mucosal barrier function during infection and emphasized the importance of TLR-dependent inflammatory responses of the respiratory epithelium.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Numerous in vitro studies have been performed to gain insight into the immune functions of respiratory epithelial cells (9,10,26,30,37). Respiratory epithelial cells in culture are capable of recognizing microbes through pattern recognition receptors such as Toll-like receptors (TLRs).…”

mentioning

confidence: 99%

Early Bacterial Colonization Induces Toll-Like Receptor-Dependent Transforming Growth Factor β Signaling in the Epithelium

Beißwenger¹,

Лысенко²,

Weiser

2009

Infect Immun

View full text Add to dashboard Cite

show abstract

“…This pattern of expression is highly correlated with the presence of gross inflammatory lesions (18)(19)(20)(21)(22)(23)(24)(25)(26). Epithelial cells also are known to express chemokines and inflammatory cytokines associated with leukocyte recruitment and activation (27). For example, Mycoplasma genitalium infection of cultured human endocervical epithelial cells revealed the expression of IL-6, IL-7, IL-8, monocyte chemoattractant protein 1 (MCP-1), and granulocyte-macro-phage colony-stimulating factor (GM-CSF) mRNA (28)(29)(30).…”

mentioning

confidence: 99%

Interaction of Mycoplasma gallisepticum with Chicken Tracheal Epithelial Cells Contributes to Macrophage Chemotaxis and Activation

Majumder

Silbart

2016

Infect Immun

View full text Add to dashboard Cite

Mycoplasma gallisepticum colonizes the chicken respiratory mucosa and mediates a severe inflammatory response hallmarked by subepithelial leukocyte infiltration. We recently reported that the interaction of M. gallisepticum with chicken tracheal epithelial cells (TECs) mediated the upregulation of chemokine and inflammatory cytokine genes in these cells (S. Majumder, F. Zappulla, and L. K. Silbart, PLoS One 9:e112796, http://dx.doi.org/10.1371/journal.pone.0112796). The current study extends these observations and sheds light on how this initial interaction may give rise to subsequent inflammatory events. Conditioned medium from TECs exposed to the virulent R low strain induced macrophage chemotaxis to a much higher degree than the nonvirulent R high strain. Coculture of chicken macrophages (HD-11) with TECs exposed to live mycoplasma revealed the upregulation of several proinflammatory genes associated with macrophage activation, including interleukin-1␤ (IL-1␤), IL-6, IL-8, CCL20, macrophage inflammatory protein 1␤ (MIP-1␤), CXCL-13, and RANTES. The upregulation of these genes was similar to that observed upon direct contact of HD-11 cells with live M. gallisepticum. Coculture of macrophages with R low -exposed TECs also resulted in prolonged expression of chemokine genes, such as those encoding CXCL-13, MIP-1␤, RANTES, and IL-8. Taken together, these studies support the notion that the initial interaction of M. gallisepticum with host respiratory epithelial cells contributes to macrophage chemotaxis and activation by virtue of robust upregulation of inflammatory cytokine and chemokine genes, thereby setting the stage for chronic tissue inflammation. Mycoplasma gallisepticum is known primarily as an extracellular pathogen; however, evidence of invasion into nonphagocytic cells, including red blood cells, HeLa cells, and fibroblasts (1-6) has been reported. The primary site of M. gallisepticum attachment and colonization is the respiratory epithelium, and the organism appears to remain localized to the mucosal surface with little or no classical invasion (7). Previous studies in our laboratory using immunohistochemistry (see Fig. S1 in the supplemental material) and in situ hybridization with a M. gallisepticumspecific 16S riboprobe suggest that the organism is confined to the luminal surface of the tracheal epithelium for four or more days postinfection (see Fig. S2). Upon colonization, mycoplasma mediates a vigorous inflammatory response initially comprised of heterophils and macrophages, followed later by infiltrating lymphocytes, including both B and T cells, into the mucosa. Previous studies indicated that macrophages play a significant role in mycoplasma clearance via phagocytosis, whereas polymorphonuclear leukocytes may aid in the dissemination of mycoplasma to other tissues (8, 9). Both B and T cells also are known to play critical roles in clearance and the prevention of dissemination of mycoplasma (9-11). However, although these events are important in antimycoplasmal defense, the dysregulated accumu...

show abstract

“…From the standpoint of antimicrobial resistance, there is the prospect that nitrosative stress/reactive nitrogen could, in vivo, provide a selective pressure for MexEF-OprNproducing multidrug-resistant mutants. Airway epithelial cells are, for example, known to produce NO upon stimulation by bacteria and bacterial products (e.g., lipopolysaccharide [LPS]) (14), and a previously reported in vitro transcriptome study of P. aeruginosa exposed to normal human epithelial cells revealed that mexEF-oprN (and mexS) was substantially upregulated (11). In addition, the observation that several genes identified previously as being members of a MexT regulon are induced in response to nitrosative stress suggests that MexT targets are components of a nitrosative stress response in P. aeruginosa.…”

mentioning

confidence: 99%

mexEF-oprN Multidrug Efflux Operon of Pseudomonas aeruginosa : Regulation by the MexT Activator in Response to Nitrosative Stress and Chloramphenicol

Fetar

Gilmour

Klinoski

et al. 2011

Antimicrob Agents Chemother

112

View full text Add to dashboard Cite

A null mutation in the mexS gene of Pseudomonas aeruginosa yielded an increased level of expression of a 3-gene operon containing a gene, xenB, whose product is highly homologous to a xenobiotic reductase in Pseudomonas fluorescens shown previously to remove nitro groups from trinitrotoluene and nitroglycerin (D. S. Blehert, B. G. Fox, and G. H. Chambliss, J. Bacteriol. 181:6254, 1999). This expression, which paralleled an increase in mexEF-oprN expression in the same mutant, was, like mexEF-oprN, dependent on the MexT LysR family positive regulator previously implicated in mexEF-oprN expression. As nitration is a well-known result of nitrosative stress, a role for xenB (and the coregulated mexEF-oprN) in a nitrosative stress response was hypothesized and tested. Using s-nitrosoglutathione (GSNO) as a source of nitrosative stress, the expression of xenB and mexEF-oprN was shown to be GSNO inducible, although in the case of xenB, this was seen only for a mutant lacking MexEF-OprN. In both instances, this GSNO-inducible expression was dependent upon MexT. Chloramphenicol, a nitroaromatic antimicrobial that is a substrate for MexEF-OprN, was shown to induce mexEF-oprN but not xenB, again dependent upon the MexT regulator, possibly because it resembles a nitrosated nitrosative stress product accommodated by MexEF-OprN.Pseudomonas aeruginosa is an opportunistic human pathogen characterized by an innate resistance to multiple antimicrobials (15), a resistance that is increasingly attributable to the operation of broadly specific, tripartite multidrug efflux systems of the resistance-nodulation-division (RND) family (39,40). Several RND family multidrug efflux systems have been described for P. aeruginosa, although the major systems contributing to intrinsic and/or acquired multidrug resistance include MexAB-OprM, MexXY-OprM, 40). Unlike MexAB-OprM and MexXYOprM, which contribute to intrinsic resistance (1,7,26,32), the MexEF-OprN and MexCD-OprJ systems are typically quiescent in wild-type cells (under usual laboratory growth conditions) (19,28,50), with expression and, therefore, a contribution to antimicrobial resistance following a mutational upregulation of the efflux genes (13,20,30,41,48). In the case of MexEF-OprN, this involves the reversion of mutations present in the mexT gene of a number of so-called wild-type strains (29, 30) or a mutation of the mexS gene (also known as qrh [25]), encoding an oxidoreductase of unknown function (48). mexT, which occurs upstream of mexEF-oprN and downstream of mexS, encodes a LysR family positive regulator that promotes mexEF-oprN (25,28,36) and mexS (25) expression. mexEF-oprN expression and modest multidrug resistance have also been reported for a mutant disrupted in the mvaT gene (53), encoding a global regulator of virulence gene expression (8).Originally identified as a determinant of fluoroquinolone resistance (12, 13), MexEF-OprN accommodates a variety of antimicrobials, including trimethoprim and chloramphenicol (28), with chloramphenicol readily selecting multidrug-...

show abstract

Airway epithelial cell signaling in response to bacterial pathogens

Cited by 64 publications

References 105 publications

Early Bacterial Colonization Induces Toll-Like Receptor-Dependent Transforming Growth Factor β Signaling in the Epithelium

Early Bacterial Colonization Induces Toll-Like Receptor-Dependent Transforming Growth Factor β Signaling in the Epithelium

Interaction of Mycoplasma gallisepticum with Chicken Tracheal Epithelial Cells Contributes to Macrophage Chemotaxis and Activation

mexEF-oprN Multidrug Efflux Operon of Pseudomonas aeruginosa : Regulation by the MexT Activator in Response to Nitrosative Stress and Chloramphenicol

Contact Info

Product

Resources

About