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Published on: July 26, 2017
Pathogen-specific TLR signaling in mucosa: mutual contribution of microbial TLR agonists and virulence factors
Jean-Claude Sirard1, Mariela Bayardo, Arnaud Didierlaurent
1INSERM, Avenir Anti-microbial mucosal Immunity - E364, Campus Pasteur - Lille, France. Jean-Claude.Sirard@ibl.fr
Abstract:
Detection of microorganisms through microbe-associated molecular patterns (MAMP) by Toll-like receptors (TLR) is crucial to trigger protective immunity. In the mucosa, sentinel cells are exposed to MAMP from both pathogens and commensals; however, the TLR response is tightly controlled to avoid inflammation in response to commensals. Uropathogenic Escherichia coli (UPEC) trigger innate responses during urinary tract infection in a TLR4-dependent and CD14-independent manner. UPEC express virulence factors, such as type 1 fimbriae and/or P fimbriae, allowing bacterial attachment to the epithelium. In this issue of the European Journal of Immunology, Fisher et al. show that fimbriae are required to induce a TLR4-specific epithelial response. Depending on the fimbriae expressed by UPEC, different adaptor molecules are involved in TLR4 signaling. These data add to the recent body of evidence suggesting that TLR responses are regulated by co-receptors, such as receptors for virulence factors. In conclusion, the "pathogenic" TLR stimulation provides a novel way for the host to ignore commensal bacteria.
Insights
Toll-like receptor (TLR) signaling, crucial for immunity, is modulated by bacterial fimbriae during urinary tract infections. Uropathogenic E. coli (UPEC) fimbriae dictate specific TLR4 adaptor molecules, enabling pathogen recognition while tolerating commensals.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Microbe-associated molecular patterns (MAMPs) detected by Toll-like receptors (TLRs) initiate protective immunity.
- Mucosal immune responses must distinguish between pathogens and commensals to prevent inflammation.
- Uropathogenic Escherichia coli (UPEC) triggers innate immunity via TLR4 in a CD14-independent manner during urinary tract infections.
Purpose of the Study:
- To investigate the role of UPEC virulence factors, specifically fimbriae, in modulating TLR4-mediated epithelial responses.
- To elucidate how different UPEC fimbriae influence TLR4 signaling pathways and adaptor molecule recruitment.
Main Methods:
- The study likely involved in vitro assays using epithelial cells and UPEC strains with defined fimbrial expression.
- Analysis of TLR4 signaling pathway activation and adaptor molecule involvement in response to different UPEC fimbriae.
Main Results:
- UPEC fimbriae are essential for inducing a TLR4-specific epithelial response.
- The type of fimbriae expressed by UPEC determines the recruitment of distinct adaptor molecules in TLR4 signaling.
- This suggests a mechanism where bacterial virulence factors act as co-receptors to fine-tune TLR responses.
Conclusions:
- TLR responses are actively regulated by co-receptors, including receptors for bacterial virulence factors.
- Pathogen-specific TLR stimulation, influenced by virulence factors like fimbriae, allows the host immune system to differentiate and tolerate commensal bacteria.
- This provides a novel mechanism for maintaining mucosal homeostasis during infection.
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