Helicobacter pylori flagellin: TLR5 evasion and fusion-based conversion into a TLR5 agonist

Kim, Jee-Hyeon; Namgung, Byeol; Jeon, Yeong Jeong; Song, Wan Seok; Lee, Jeonghyun; Kang, Seung Goo; Yoon, Sung‐il

doi:10.1016/j.bbrc.2018.09.179

Cited by 15 publications

(12 citation statements)

References 22 publications

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“…We also found in FlaB the consensus in the D0 domain involved in the flagellin/TLR5 complex stabilization ( Figures 6A,C ). We compared the leptospiral FlaB sequences in these 3 consensus binding TLR5 regions with other spirochetes, Borrelia burgdorferi and Treponema spp., the latter known to signal via TLR5 when FlaB are expressed as recombinant proteins ( 42 ) and also with bacteria known to dodge the TLR5 response such as Helicobacter pylori ( 43 ) and Bartonella bacilliformis ( 10 ), presenting variations in those consensus sequences of their flagellins ( Supplementary Figure 4A ). In addition, we also found this FlaB region to be 100% conserved in a panel of major species of Leptospira circulating all over the world, including potential human pathogens, such as L. borgpeterseni, L. kirschneri , L. noguchii , L. weilii , L. santarosai , as well as L. licerasiae , belonging to another clade of species of lower virulence ( 2 ) ( Supplementary Figure 4B ).…”

Section: Resultsmentioning

confidence: 99%

“…In conclusion, we showed here that pathogenic Leptospira largely escape recognition by TLR5. Other bacteria such as Helicobacter pylori have been shown to escape the TLR5 response through modification of the amino residues in the D0 or D1 regions of flagellin subunits (43), but leptospires seem to differ in avoiding TLR5 recognition. Indeed, our data demonstrate that the endoflagella play a role in the escape from TLR5 surveillance, which has never been shown before and might hold true for other spirochetes.…”

Section: Discussionmentioning

confidence: 99%

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Escape of TLR5 Recognition by Leptospira spp.: A Rationale for Atypical Endoflagella

et al. 2020

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Holzapfel et al. TLR5 Evasion by Leptospires the FlaB, but not the FlaA subunits. Altogether, in contrast to different bacteria that modify their flagellin sequences to escape TLR5 recognition, our study suggests that the peculiar central localization and stability of the FlaB monomers in the periplasmic endoflagellae, associated with the downregulation of FlaB subunits in hosts, constitute an efficient strategy of leptospires to escape the TLR5 recognition and the induced immune response.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Escape of TLR5 Recognition by Leptospira spp.: A Rationale for Atypical Endoflagella

et al. 2020

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“…H. pylori flagellin seems to be a less potent stimulator compared with other flagellins[ 28 ] but has a significant role in long-term bacterial persistence. The lack of TLR5 activity in response to H. pylori flagellin is caused mainly by the amino acid residues variation R89, L93, and E114 described as hotspots for binding TLR5 which, replaced with threonine (R89T), lysine (L93K), and aspartate (E114D) in H. pylori flagellin, lead to receptor evasion[ 29 ]. TLR5 instead recognizes CagL and CagY, two proteins from the type IV secretion system (T4SS) of H. pylori , and both have immunoregulatory properties[ 30 , 31 ].…”

Section: Starters and Mediators Of The Innate Immune Response In Gast...mentioning

confidence: 99%

Intersections between innate immune response and gastric cancer development

Villarroel‐Espíndola¹,

Ejsmentewicz²,

González-Stegmaier³

et al. 2023

World J Gastroenterol

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Worldwide, gastric cancer (GC) is the fifth most commonly diagnosed malignancy. It has a reduced prevalence but has maintained its poor prognosis being the fourth leading cause of deaths related to cancer. The highest mortality rates occur in Asian and Latin American countries, where cases are usually diagnosed at advanced stages. Overall, GC is viewed as the consequence of a multifactorial process, involving the virulence of the Helicobacter pylori ( H. pylori ) strains, as well as some environmental factors, dietary habits, and host intrinsic factors. The tumor microenvironment in GC appears to be chronically inflamed which promotes tumor progression and reduces the therapeutic opportunities. It has been suggested that inflammation assessment needs to be measured qualitatively and quantitatively, considering cell-infiltration types, availability of receptors to detect damage and pathogens, and presence or absence of aggressive H. pylori strains. Gastrointestinal epithelial cells express several Toll-like receptors and determine the first defensive line against pathogens, and have been also described as mediators of tumorigenesis. However, other molecules, such as cytokines related to inflammation and innate immunity, including immune checkpoint molecules, interferon-gamma pathway and NETosis have been associated with an increased risk of GC. Therefore, this review will explore innate immune activation in the context of premalignant lesions of the gastric epithelium and established gastric tumors.

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“…Modification of the lipid A portion of LPS is used by H. pylori to escape immune recognition of TLR4 and evade the host innate immune response ( 119 ). Another example of evasion of recognition of PRRs is flagellin, which can be detected by TLR5 ( 120 ). H. pylori does not release flagellin, and the flagellin of H. pylori is less pro-inflammatory than that of Salmonella typhimurium ( 121 ).…”

Section: Innate Immune Responses In Gcmentioning

confidence: 99%

Roles of Plasmacytoid Dendritic Cells in Gastric Cancer

et al. 2022

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Gastric cancer (GC) is the fifth most common neoplasm and the third most deadly cancer in humans worldwide. Helicobacter pylori infection is the most important causative factor of gastric carcinogenesis, and activates host innate and adaptive immune responses. As key constituents of the tumor immune microenvironment, plasmacytoid dendritic cells (pDCs) are increasingly attracting attention owing to their potential roles in immunosuppression. We recently reported that pDCs have vital roles in the development of immunosuppression in GC. Clarifying the contribution of pDCs to the development and progression of GC may lead to improvements in cancer therapy. In this review, we summarize current knowledge regarding immune modulation in GC, especially the roles of pDCs in GC carcinogenesis and treatment strategies.

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Helicobacter pylori flagellin: TLR5 evasion and fusion-based conversion into a TLR5 agonist

Cited by 15 publications

References 22 publications

Escape of TLR5 Recognition by Leptospira spp.: A Rationale for Atypical Endoflagella

Escape of TLR5 Recognition by Leptospira spp.: A Rationale for Atypical Endoflagella

Intersections between innate immune response and gastric cancer development

Roles of Plasmacytoid Dendritic Cells in Gastric Cancer

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