Published online before print November 12, 2008

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(Journal of Leukocyte Biology. 2009;85:225-234.)
© 2009 Society for Leukocyte Biology

Salmonella induces death of CD8⁺ dendritic cells but not CD11c^intCD11b⁺ inflammatory cells in vivo via MyD88 and TNFR1

Department of Microbiology and Immunology, Göteborg University, Göteborg, Sweden

¹ Correspondence: Department of Microbiology and Immunology, Göteborg University, Box 435, SE 405 30 Göteborg, Sweden. E-mail: mary-jo.wick{at}immuno.gu.se

ABSTRACT

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 CD8⁺ DCs were sensitive to Salmonella-induced death, CD8^– DCs and in particular recruited CD11c^intCD11b⁺ inflammatory cells, were resistant. Infecting mice deficient for MyD88 revealed that Salmonella-induced death of CD8⁺ DCs was dependent on this adaptor for TLR signaling. In addition, CD8⁺ 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^intCD11b⁺ 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^intCD11b⁺ 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.

Key Words: oral infection • mesenteric lymph nodes • Toll-like receptor

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