The Campylobacter jejuni CiaD effector protein activates MAP kinase signaling pathways and is required for the development of disease.
| Title: | The Campylobacter jejuni CiaD effector protein activates MAP kinase signaling pathways and is required for the development of disease. |
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| Authors: | Samuelson DR; Eucker TP; Bell JA; Dybas L; Mansfield LS; Konkel ME; School of Molecular Biosciences, Washington State University, College of Veterinary Medicine, Life Sciences Bldg, Room 302c, Pullman, WA 99164-7520, USA. konkel@vetmed.wsu.edu. |
| Source: | Cell communication and signaling : CCS [Cell Commun Signal] 2013 Oct 21; Vol. 11, pp. 79. Date of Electronic Publication: 2013 Oct 21. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| Language: | English |
| Journal Info: | Publisher: BioMed Central Country of Publication: England NLM ID: 101170464 Publication Model: Electronic Cited Medium: Internet ISSN: 1478-811X (Electronic) Linking ISSN: 1478811X NLM ISO Abbreviation: Cell Commun Signal Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : BioMed Central, c2003- |
| MeSH Terms: | MAP Kinase Signaling System*; Bacterial Proteins/*metabolism ; Campylobacter Infections/*metabolism ; Campylobacter jejuni/*physiology ; Virulence Factors/*metabolism; Bacterial Proteins/genetics ; Campylobacter Infections/microbiology ; Campylobacter jejuni/pathogenicity ; Flagella/metabolism ; Interleukin-10/genetics ; Interleukin-8/metabolism ; Virulence Factors/genetics ; Animals ; Binding Sites ; Cell Line ; Humans ; Mice ; Mice, Knockout ; Mutation |
| Abstract: | Background: Enteric pathogens utilize a distinct set of proteins to modulate host cell signaling events that promote host cell invasion, induction of the inflammatory response, and intracellular survival. Human infection with Campylobacter jejuni, the causative agent of campylobacteriosis, is characterized by diarrhea containing blood and leukocytes. The clinical presentation of acute disease, which is consistent with cellular invasion, requires the delivery of the Campylobacter invasion antigens (Cia) to the cytosol of host cells via a flagellar Type III Secretion System (T3SS). We identified a novel T3SS effector protein, which we termed CiaD that is exported from the C. jejuni flagellum and delivered to the cytosol of host cells.; Results: We show that the host cell kinases p38 and Erk 1/2 are activated by CiaD, resulting in the secretion of interleukin-8 (IL-8) from host cells. Additional experiments revealed that CiaD-mediated activation of p38 and Erk 1/2 are required for maximal invasion of host cells by C. jejuni. CiaD contributes to disease, as evidenced by infection of IL-10 knockout mice. Noteworthy is that CiaD contains a Mitogen-activated protein (MAP) kinase-docking site that is found within effector proteins produced by other enteric pathogens. These findings indicate that C. jejuni activates the MAP kinase signaling pathways Erk 1/2 and p38 to promote cellular invasion and the release of the IL-8 pro-inflammatory chemokine.; Conclusions: The identification of a novel T3SS effector protein from C. jejuni significantly expands the knowledge of virulence proteins associated with C. jejuni pathogenesis and provides greater insight into the mechanism utilized by C. jejuni to invade host cells. |
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| Grant Information: | T32 GM008336 United States GM NIGMS NIH HHS; U19 AI090872 United States AI NIAID NIH HHS; T32GM083864 United States GM NIGMS NIH HHS; R56 AIO88518-01A1 United States PHS HHS; T32GM008336 United States GM NIGMS NIH HHS; U19-AI-09087 United States AI NIAID NIH HHS |
| Substance Nomenclature: | 0 (Bacterial Proteins); 0 (Interleukin-8); 0 (Virulence Factors); 130068-27-8 (Interleukin-10) |
| Entry Date(s): | Date Created: 20131023 Date Completed: 20140606 Latest Revision: 20211021 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC3833307 |
| DOI: | 10.1186/1478-811X-11-79 |
| PMID: | 24144181 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.