The Campylobacter jejuni CiaD effector protein activates MAP kinase signaling pathways and is required for the development of disease.

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.

• Authors: Derrick R Samuelson, Tyson P Eucker, Julia A Bell, Leslie Dybas, Linda S Mansfield, Michael E Konkel
• Journal: Cell communication and signaling : CCS (Cell Commun Signal) Vol. 11 Pg. 79 (Oct 21 2013) ISSN: 1478-811X [Electronic] England
• PMID: 24144181 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Bacterial Proteins
• Interleukin-8
• Virulence Factors
• Interleukin-10

Topics

• Animals
• Bacterial Proteins (genetics, metabolism)
• Binding Sites
• Campylobacter Infections (metabolism, microbiology)
• Campylobacter jejuni (pathogenicity, physiology)
• Cell Line
• Flagella (metabolism)
• Humans
• Interleukin-10 (genetics)
• Interleukin-8 (metabolism)
• MAP Kinase Signaling System
• Mice
• Mice, Knockout
• Mutation
• Virulence Factors (genetics, metabolism)