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Salmonella induces death of CD8α + dendritic cells but not CD11c int CD11b + inflammatory cells in vivo via MyD88 and TNFR1
Author(s) -
Sundquist Malin,
Wick Mary Jo
Publication year - 2009
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0708413
Subject(s) - cd11c , salmonella enterica , biology , salmonella , immune system , cd8 , immunity , acquired immune system , immunology , integrin alpha m , programmed cell death , innate immune system , microbiology and biotechnology , apoptosis , phenotype , biochemistry , genetics , gene , bacteria
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 CD8α + DCs were sensitive to Salmonella ‐induced death, CD8α – DCs and in particular recruited CD11c int CD11b + inflammatory cells, were resistant. Infecting mice deficient for MyD88 revealed that Salmonella ‐induced death of CD8α + DCs was dependent on this adaptor for TLR signaling. In addition, CD8α + 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.