Campylobacter jejuni-mediated induction of CC and CXC chemokines and chemokine receptors in human dendritic cells.

Abstract

Campylobacter jejuni is a leading worldwide bacterial cause of human diarrheal disease. Although the specific molecular mechanisms of C. jejuni pathogenesis have not been characterized in detail, host inflammatory responses are thought to be major contributing factors to the resulting typical acute colitis. The intestinal mucosal chemokine response is particularly important in the initial stages of bacterium-induced gut inflammation. Chemokines attract blood phagocytes and lymphocytes to the site of infection and regulate immune cell maturation and the development of localized lymphoid tissues. The production of chemokines by dendritic cells (DCs) following Campylobacter infection has not yet been analyzed. In the current study, we infected human monocyte-derived DCs with C. jejuni to examine the production of key proinflammatory chemokines and chemokine receptors. The chemokines, including CC families (macrophage inflammatory protein 1α [MIP-1α], MIP-1β, RANTES) and CXC families (growth-related oncogene α [GRO-α], IP-10, and monokine induced by gamma interferon [MIG]), were upregulated in Campylobacter-infected DCs. Chemokine receptors CCR6 and CCR7, with roles in DC trafficking, were also induced in Campylobacter-infected DCs. Further, Campylobacter infection stimulated the phosphorylation of P38, P44/42, and stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) mitogen-activated protein kinases (MAPKs) in DCs. NF-κB activation was specifically involved in chemokine induction in DCs infected with C. jejuni. Additionally, STAT3 was significantly increased in Campylobacter-infected DCs compared to that in uninfected DCs. These results suggest that DCs play a significant role in the initiation and modulation of the inflammatory response by enlisting monocytes, neutrophils, and T lymphocytes during human intestinal infection with Campylobacter.

• Authors: Lan Hu, Mechelle D Bray, Yansheng Geng, Dennis J Kopecko
• Journal: Infection and immunity (Infect Immun) Vol. 80 Issue 8 Pg. 2929-39 (Aug 2012) ISSN: 1098-5522 [Electronic] United States
• PMID: 22689814 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Butylamines
• CCR6 protein, human
• CCR7 protein, human
• Chemokines, CC
• Chemokines, CXC
• PD 0084430
• Phenols
• Polysaccharides
• RNA, Messenger
• Receptors, CCR6
• Receptors, CCR7
• Receptors, Chemokine
• STAT3 Transcription Factor
• STAT3 protein, human
• Mitogen-Activated Protein Kinases
• Polymyxin B

Topics

• Anti-Bacterial Agents
• Butylamines
• Campylobacter jejuni (immunology, physiology)
• Cells, Cultured
• Chemokines, CC (genetics, metabolism)
• Chemokines, CXC (genetics, metabolism)
• Dendritic Cells (drug effects, metabolism)
• Gene Expression Regulation (immunology)
• Humans
• Mitogen-Activated Protein Kinases (genetics, metabolism)
• Phenols
• Polymyxin B (pharmacology)
• Polysaccharides (immunology)
• RNA, Messenger (genetics, metabolism)
• Receptors, CCR6 (genetics, metabolism)
• Receptors, CCR7 (genetics, metabolism)
• Receptors, Chemokine (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• STAT3 Transcription Factor (genetics, metabolism)
• Time Factors