Scientific Publications by FDA Staff
Infect Immun 2012 Aug;80(8):2929-39
Campylobacter jejuni-mediated Induction of CC and CXC Chemokines and Chemokine Receptors in Human Dendritic Cells.
Hu L, Bray MD, Geng Y, Kopecko DJ
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 bacteria-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 (MIP-1alpha, MIP-1beta, RANTES) and CXC families (GRO-alpha, IP-10, and 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 SAPK/JNK MAP kinases in DCs. NF-kappaB activation was specifically involved in chemokine induction in DCs infected with C. jejuni. Additionally, STAT3 was significantly increased in Campylobacter-infected DCs compared to uninfected DCs. These results suggest that DCs play a significant role in the initiation and modulation of the inflammatory response by enlisting monocytes, neutrophilis, and T lymphocytes during human intestinal infection with Campylobacter.
|Category: Journal Article|
|PubMed ID: #22689814||DOI: 10.1128/IAI.00129-12|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2012-06-13||Entry Last Modified: 2012-10-12|