Pneumococci induced IL-8 expression in human pulmonary epithelium by TLR1 and TLR2 and Rac1

Schmeck, Bernd; Huber, Sylvia; Moog, Kerstin; Zahlten, Janine; Hocke, AC; Opitz, Bastian; Hammerschmidt, S; Mitchell, Thomas C.; Rosseau, Simone; Suttorp, N; Hippenstiel, Stefan

doi:10.1055/s-2006-932726

Cited by 2 publications

(4 citation statements)

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“…This is consistent with studies showing that p38 MAPK is activated in the TLR2 signaling cascade by bacteria (4,7,11). Blocking p38 MAPK increased the integrity of the epithelial barrier and was associated with maintenance of actin filament organization.…”

Section: Discussionsupporting

confidence: 92%

“…Numerous studies have shown that airway epithelium is capable of recognizing molecules with lipid anchors through the pattern recognition receptor TLR2. Furthermore, it is known that TLR2 is expressed and functional in airway epithelial cells and capable of recognizing and responding to pathogens (6,7,32,33). Interestingly, Muir et al (34) showed that TLR2 is expressed only at the apical surface of polarized epithelial cells such as 16HBE.…”

Section: Discussionmentioning

confidence: 99%

“…H. influenzae has been reported to induce responses through pattern recognition receptors, Tolllike receptors (TLR) 2 2 and 4, which bind its lipoproteins and lipopolysaccharide, respectively (4 -6). S. pneumoniae also interacts with TLR2 via its lipid anchored membrane components (7,8) and TLR4 via pneumolysin (9). Recognition of these bacterial products by TLRs leads to signaling events that result in activation of NFB and p38 MAP kinase (p38 MAPK) with subsequent proinflammatory responses (4,6,10,11).…”

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confidence: 99%

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Role of p38 MAP Kinase and Transforming Growth Factor-β Signaling in Transepithelial Migration of Invasive Bacterial Pathogens

Beißwenger

Coyne

Shchepetov

et al. 2007

Journal of Biological Chemistry

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Streptococcus pneumoniae and Haemophilus influenzae are human pathogens that often asymptomatically colonize the mucosal surface of the upper respiratory tract, but also occasionally cause invasive disease. The ability of these species to traverse the epithelium of the airway mucosa was modeled in vitro using polarized respiratory epithelial cells in culture. Migration across the epithelial barrier was preceded by loss of transepithelial resistance. Membrane products of S. pneumoniae that included lipoteichoic acid induced disruption of the epithelial barrier in a Toll-like receptor 2-dependent manner. This result correlates with a recent genetic study that associates increased TLR2 signaling with increased rates of invasive pneumococcal disease in humans. Loss of transepithelial resistance by the TLR2 ligand correlated with activation of p38 MAP kinase and transforming growth factor (TGF)-␤ signaling. Activation of p38 MAPK and TGF-␤ signaling in epithelial cells upon nasal infection with S. pneumoniae was also demonstrated in vivo. Inhibition of either p38 MAPK or TGF-␤ signaling was sufficient to inhibit the migration of S. pneumoniae or H. influenzae. Our data shows that diverse bacteria utilize common mechanisms, including MAPK and TGF-␤ signaling pathways to disrupt epithelial barriers and promote invasion.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Role of p38 MAP Kinase and Transforming Growth Factor-β Signaling in Transepithelial Migration of Invasive Bacterial Pathogens

Beißwenger

Coyne

Shchepetov

et al. 2007

Journal of Biological Chemistry

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“…RhoA is activated by pneumolysin (15), whereas Rac1 and Cdc42 are activated by pneumococcus serotype 2 and serotype 35A infections, respectively (17,36). To confirm the involvement of small RhoGTPases in WT and ⌬clpL pneumococcal infections, the expression of small RhoGTPases was determined in GTPase activity assays.…”

Section: Resultsmentioning

confidence: 99%

Streptococcus pneumoniae ClpL Modulates Adherence to A549 Human Lung Cells through Rap1/Rac1 Activation

Nguyen

Tran

et al. 2014

Infect Immun

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bCaseinolytic protease L (ClpL) is a member of the HSP100/Clp chaperone family, which is found mainly in Gram-positive bacteria. ClpL is highly expressed during infection for refolding of stress-induced denatured proteins, some of which are important for adherence. However, the role of ClpL in modulating pneumococcal virulence is poorly understood. Here, we show that ClpL impairs pneumococcal adherence to A549 lung cells by inducing and activating Rap1 and Rac1, thus increasing phosphorylation of cofilin (inactive form). Moreover, infection with a clpL mutant (⌬clpL) causes a greater degree of filopodium formation than D39 wild-type (WT) infection. Inhibition of Rap1 and Rac1 impairs filopodium formation and pneumococcal adherence. Therefore, ClpL can reduce pneumococcal adherence to A549 cells, likely via modulation of Rap1-and Rac1-mediated filopodium formation. These results demonstrate a potential role for ClpL in pneumococcal resistance to host cell adherence during infection. This study provides insight into further understanding the interactions between hosts and pathogens.

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Pneumococci induced IL-8 expression in human pulmonary epithelium by TLR1 and TLR2 and Rac1

Cited by 2 publications

References 0 publications

Role of p38 MAP Kinase and Transforming Growth Factor-β Signaling in Transepithelial Migration of Invasive Bacterial Pathogens

Role of p38 MAP Kinase and Transforming Growth Factor-β Signaling in Transepithelial Migration of Invasive Bacterial Pathogens

Streptococcus pneumoniae ClpL Modulates Adherence to A549 Human Lung Cells through Rap1/Rac1 Activation

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