Salmonella induces death of CD8a super(+) dendritic cells but not CD11c super(int)CD11b super(+) inflammatory cells in vivo via MyD88 and TNFR1

• Published in: Journal of leukocyte biology Vol. 85; no. 2; pp. 225 - 234
• Main Authors: Sundquist, M, Wick, MJ
• Format: Journal Article
• Language: English
• Published: 01.02.2009
• Subjects: Salmonella
• ISSN: 0741-5400
• DOI: 10.1189/jlb.0708413

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 enterlca serovar Typhimurium induces death of DCs in the gut-draining lymph nodes. Although CD8a super(+) DCs were sensitive to Salmonella-induced death, CD8a super(-) DCs and in particular recruited CD11c super(int)CD11b super(+) inflammatory cells, were resistant. Infecting mice deficient for MyD88 revealed that Salmonella-induced death of CD8a super(+) DCs was dependent on this adaptor for TLR signaling. In addition, CD8a super(+) 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 super(int)CD11b super(+) 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 super(int)CD11b super(+) cells could not present the model antigen OVA expressed in Salmonella to OVA-speciflc 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.