Cutting Edge: Bacterial Flagellin Activates Basolaterally Expressed TLR5 to Induce Epithelial Proinflammatory Gene Expression
Reads0
Chats0
TLDR
Investigating how epithelia detect flagellin revealed that cell surface expression of Toll-like receptor 5 (TLR5) conferred NF-κB gene expression in response to flageLLin, providing a molecular basis for the polarity of this innate immune response.Abstract:
Flagellin, the structural component of bacterial flagella, is secreted by pathogenic and commensal bacteria. Flagellin activates proinflammatory gene expression in intestinal epithelia. However, only flagellin that contacts basolateral epithelial surfaces is proinflammatory; apical flagellin has no effect. Pathogenic Salmonella, but not commensal Escherichia coli, translocate flagellin across epithelia, thus activating epithelial proinflammatory gene expression. Investigating how epithelia detect flagellin revealed that cell surface expression of Toll-like receptor 5 (TLR5) conferred NF-kappaB gene expression in response to flagellin. The response depended on both extracellular leucine-rich repeats and intracellular Toll/IL-1R homology region of TLR5 as well as the adaptor protein MyD88. Furthermore, immunolocalization and cell surface-selective biotinylation revealed that TLR5 is expressed exclusively on the basolateral surface of intestinal epithelia, thus providing a molecular basis for the polarity of this innate immune response. Thus, detection of flagellin by basolateral TLR5 mediates epithelial-driven inflammatory responses to Salmonella.read more
Citations
More filters
Journal ArticleDOI
Toll-like receptors.
TL;DR: This unit discusses mammalian Toll receptors (TLR1‐10) that have an essential role in the innate immune recognition of microorganisms and are discussed are TLR‐mediated signaling pathways and antibodies that are available to detect specific TLRs.
Journal ArticleDOI
Toll-like receptors and innate immunity
TL;DR: This work has shown that activation of inflammatory and antimicrobial innate immune responses through recognition of Toll-like receptors expressed on dendritic cells triggers functional maturation of dendrites and leads to initiation of antigen-specific adaptive immune responses.
Journal ArticleDOI
Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis
Seth Rakoff-Nahoum,Justin C. Paglino,Fatima Eslami-Varzaneh,Stephen C. Edberg,Ruslan Medzhitov +4 more
TL;DR: It is shown that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis and protection from injury.
Journal ArticleDOI
Toll-like receptors in innate immunity.
Kiyoshi Takeda,Shizuo Akira +1 more
TL;DR: Toll-like receptors-mediated activation of innate immunity controls not only host defense against pathogens but also immune disorders, and the involvement of TLR-mediated pathways in autoimmune and inflammatory diseases has been proposed.
Journal ArticleDOI
The two NF-κB activation pathways and their role in innate and adaptive immunity
Giuseppina Bonizzi,Michael Karin +1 more
TL;DR: Results strongly suggest that the classical and alternative pathways to NF-κB activation have distinct regulatory functions, one that is mostly involved in innate immunity and the other in adaptive immunity.
References
More filters
Journal ArticleDOI
The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5.
Fumitaka Hayashi,Kelly D. Smith,Adrian Ozinsky,Thomas R. Hawn,Thomas R. Hawn,Eugene C. Yi,David R. Goodlett,Jimmy K. Eng,Shizuo Akira,David M. Underhill,Alan Aderem +10 more
TL;DR: It is reported that mammalian TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and that activation of the receptor mobilizes the nuclear factor NF-κB and stimulates tumour necrosis factor-α production, and the data suggest thatTLR5, a member of the evolutionarily conserved Toll-like receptor family, has evolved to permit mammals specifically to detect flageLLated bacterial pathogens.
Journal ArticleDOI
Targeted Disruption of the MyD88 Gene Results in Loss of IL-1- and IL-18-Mediated Function
Osamu Adachi,Taro Kawai,Kiyoshi Takeda,Makoto Matsumoto,Hiroko Tsutsui,Masafumi Sakagami,Kenji Nakanishi,Shizuo Akira +7 more
TL;DR: It is demonstrated that MyD88 is a critical component in the signaling cascade that is mediated by IL-1 receptor as well as IL-18 receptor, and increases in interferon-gamma production and natural killer cell activity in response to IL- 18 are abrogated.
Journal ArticleDOI
MyD88 Is an Adaptor Protein in the hToll/IL-1 Receptor Family Signaling Pathways
Ruslan Medzhitov,Paula Preston-Hurlburt,Elizabeth Kopp,Andrew Stadlen,Chaoqun Chen,Sankar Ghosh,Charles A. Janeway +6 more
TL;DR: MyD88 is implicate as a general adaptor/regulator molecule for the Toll/IL-1R family of receptors for innate immunity and induces activation of NF-kappaB via the Pelle-like kinase IRAK and the TRAF6 protein, similar to IL- 1R-mediated NF- kappaB activation.
Journal ArticleDOI
Epithelial cells secrete the chemokine interleukin-8 in response to bacterial entry
TL;DR: The novel concept that epithelial cells serve as an early signaling system to host immune and inflammatory cells in the underlying mucosa following bacterial entry is suggested.
Journal ArticleDOI
Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response
Andrew T. Gewirtz,Peter O. Simon,Clare K. Schmitt,Laura J. Taylor,Curt H. Hagedorn,Alison D. O'Brien,Andrew S. Neish,James L. Madara +7 more
TL;DR: Findings indicate that translocation of flagellin across epithelia, subsequent to apical epithelial-S.