Salmonella induces death of CD8alpha(+) dendritic cells but not CD11c(int)CD11b(+) inflammatory cells in vivo via MyD88 and TNFR1.

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

Animals

Antigen Presentation

immunology

Antigens

CD11b

immunology

Antigens

CD11c

immunology

Antigens

CD8

immunology

CD4-Positive T-Lymphocytes

immunology

Cell Count

Cell Death

Dendritic Cells

cytology

immunology

microbiology

Green Fluorescent Proteins

metabolism

Inflammation

immunology

microbiology

Lymph Nodes

cytology

immunology

microbiology

Mice

Mice

Inbred C57BL

Myeloid Differentiation Factor 88

deficiency

immunology

Receptors

Tumor Necrosis Factor

Type I

immunology

Salmonella Infections

immunology

Salmonella enterica

immunology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)