PMID- 19004989 OWN - NLM STAT- MEDLINE DCOM- 20090311 LR - 20171116 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 85 IP - 2 DP - 2009 Feb TI - Salmonella induces death of CD8alpha(+) dendritic cells but not CD11c(int)CD11b(+) inflammatory cells in vivo via MyD88 and TNFR1. PG - 225-34 LID - 10.1189/jlb.0708413 [doi] AB - Dendritic cells (DCs), whose lifespan influences their ability to stimulate the immune system, are potent APCs that are critical for initiating immunity. Here, we show that oral infection with Salmonella enterica serovar Typhimurium induces death of DCs in the gut-draining lymph nodes. Although CD8alpha(+) DCs were sensitive to Salmonella-induced death, CD8alpha(-) DCs and in particular recruited CD11c(int)CD11b(+) inflammatory cells, were resistant. Infecting mice deficient for MyD88 revealed that Salmonella-induced death of CD8alpha(+) DCs was dependent on this adaptor for TLR signaling. In addition, CD8alpha(+) DCs in infected, TNFR1-deficient mice were resistant to Salmonella-induced death. These data, combined with the strict MyD88-dependent production of TNF in Salmonella-infected mice, suggest that MyD88-dependent TNF mediates DC death. As recruited CD11c(int)CD11b(+) cells were resistant to Salmonella-induced death, they could compensate for the infection-induced loss of DCs if they function as APCs. However, in contrast to DCs, CD11c(int)CD11b(+) cells could not present the model antigen OVA expressed in Salmonella to OVA-specific CD4 T cells. These results show that Salmonella induces DC death after oral infection via MyD88 and TNFR1, which could have a negative impact on the initiation of antibacterial immunity. FAU - Sundquist, Malin AU - Sundquist M AD - Department of Microbiology and Immunology, Goteborg University, Goteborg, Sweden. FAU - Wick, Mary Jo AU - Wick MJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20081112 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (CD11b Antigen) RN - 0 (CD11c Antigen) RN - 0 (CD8 Antigens) RN - 0 (CD8 antigen, alpha chain) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Receptors, Tumor Necrosis Factor, Type I) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Animals MH - Antigen Presentation/immunology MH - CD11b Antigen/*immunology MH - CD11c Antigen/*immunology MH - CD4-Positive T-Lymphocytes/immunology MH - CD8 Antigens/*immunology MH - Cell Count MH - Cell Death MH - Dendritic Cells/*cytology/immunology/microbiology MH - Green Fluorescent Proteins/metabolism MH - Inflammation/immunology/microbiology MH - Lymph Nodes/cytology/immunology/microbiology MH - Mice MH - Mice, Inbred C57BL MH - Myeloid Differentiation Factor 88/deficiency/*immunology MH - Receptors, Tumor Necrosis Factor, Type I/*immunology MH - Salmonella Infections/immunology MH - Salmonella enterica/*immunology EDAT- 2008/11/14 09:00 MHDA- 2009/03/12 09:00 CRDT- 2008/11/14 09:00 PHST- 2008/11/14 09:00 [pubmed] PHST- 2009/03/12 09:00 [medline] PHST- 2008/11/14 09:00 [entrez] AID - jlb.0708413 [pii] AID - 10.1189/jlb.0708413 [doi] PST - ppublish SO - J Leukoc Biol. 2009 Feb;85(2):225-34. doi: 10.1189/jlb.0708413. Epub 2008 Nov 12.