PMID- 18397382 OWN - NLM STAT- MEDLINE DCOM- 20080924 LR - 20230425 IS - 1462-5822 (Electronic) IS - 1462-5814 (Print) IS - 1462-5814 (Linking) VI - 10 IP - 8 DP - 2008 Aug TI - Nramp1 expression by dendritic cells modulates inflammatory responses during Salmonella Typhimurium infection. PG - 1646-61 LID - 10.1111/j.1462-5822.2008.01155.x [doi] AB - Host resistance against Salmonella enterica serovar Typhimurium (S. Typhimurium) is mediated by natural resistance-associated macrophage protein 1 (Nramp1/Slc11a1). Nramp1 is critical to host defence, as mice lacking Nramp1 fail to control bacterial replication and succumb to low doses of S. Typhimurium. Despite this crucial role, the mechanisms underlying Nramp1's protective effects are unclear. Dendritic cells (DCs) that sample the intestinal lumen are among the first cells encountered by S. Typhimurium following oral infection and act as a conduit for S. Typhimurium to cross the intestinal epithelial barrier. We report that DCs, including intestinal, splenic and bone marrow-derived DCs (BMDCs), express Nramp1 protein. In the small intestine, Nramp1 expression is greater in a subset of DCs (CD11c(+)CD103(-)) characterized by the elevated expression of pro-inflammatory cytokines in response to bacterial products. While Nramp1 expression did not affect S. Typhimurium replication in BMDCs, infected Nramp1+/+ BMDCs and intestinal CD11c(+)CD103(-) DCs secreted more inflammatory cytokines (IL-6, IL-12 and TNF-alpha) than Nramp1-/-, suggesting that Nramp1 expression may promote a more rapid inflammatory response following infection. Collectively, these findings reveal a new role for DCs and Nramp1 in modulating the host inflammatory response to S. Typhimurium. FAU - Valdez, Yanet AU - Valdez Y AD - Michael Smith Laboratories, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. FAU - Diehl, Gretchen E AU - Diehl GE FAU - Vallance, Bruce A AU - Vallance BA FAU - Grassl, Guntram A AU - Grassl GA FAU - Guttman, Julian A AU - Guttman JA FAU - Brown, Nat F AU - Brown NF FAU - Rosenberger, Carrie M AU - Rosenberger CM FAU - Littman, Dan R AU - Littman DR FAU - Gros, Philippe AU - Gros P FAU - Finlay, B Brett AU - Finlay BB LA - eng GR - HHMI/Howard Hughes Medical Institute/United States GR - 5R01 AI033856/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080407 PL - India TA - Cell Microbiol JT - Cellular microbiology JID - 100883691 RN - 0 (Cation Transport Proteins) RN - 0 (Cytokines) RN - 0 (natural resistance-associated macrophage protein 1) SB - IM MH - Animals MH - Cation Transport Proteins/*immunology MH - Cytokines/immunology MH - Dendritic Cells/*immunology MH - Intestine, Small/microbiology MH - Mice MH - Mucous Membrane/immunology MH - Salmonella Infections, Animal/*immunology MH - Salmonella typhimurium/*immunology PMC - PMC3051341 MID - NIHMS89629 OID - NLM: HHMIMS89629 EDAT- 2008/04/10 09:00 MHDA- 2008/09/25 09:00 PMCR- 2011/03/09 CRDT- 2008/04/10 09:00 PHST- 2008/04/10 09:00 [pubmed] PHST- 2008/09/25 09:00 [medline] PHST- 2008/04/10 09:00 [entrez] PHST- 2011/03/09 00:00 [pmc-release] AID - CMI1155 [pii] AID - 10.1111/j.1462-5822.2008.01155.x [doi] PST - ppublish SO - Cell Microbiol. 2008 Aug;10(8):1646-61. doi: 10.1111/j.1462-5822.2008.01155.x. Epub 2008 Apr 7.