Salmonella typhimurium infection triggers dendritic cells and macrophages to adopt distinct migration patterns in vivo.
The presence of an anti-bacterial T cell response and evidence of bacterial products in inflamed joints of reactive arthritis patients suggests an antigen transportation role in this disease for macrophages and dendritic cells. We have investigated the functional properties and in vivo migration of macrophages and DC after infection with Salmonella enterica serovar Typhimurium (S. typhimurium). BM-derived macrophages and DC displayed enhanced expression of costimulatory molecules (CD40 and CD86) and increased production of pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-12p40) and nitric oxide after infection. Upon adoptive transfer into mice, infected DC migrated to lymphoid tissues and induced an anti-Salmonella T cell response, whereas infected macrophages did not. Infection of DC with S. typhimurium was associated with strong up-regulation of the chemokine receptor CCR7 and acquisition of responsiveness to chemokines acting through this receptor. Moreover, S. typhimurium-infected CCR7-deficient DC were unable to migrate to lymph nodes after adoptive transfer, although they did reach the spleen. Our data demonstrate distinct roles for macrophages and DC as antigen transporters after S. typhimurium infection and a dependence on CCR7 for migration of DC to lymph nodes after bacterial infection.
Zhao
Chunfang
C
The Edward Jenner Institute for Vaccine Research, Compton, Newbury, UK.
Wood
Michael W
MW
Galyov
Edouard E
EE
Höpken
Uta E
UE
Lipp
Martin
M
Bodmer
Helen C
HC
Tough
David F
DF
Carter
Robert W
RW
D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology / Q000637:transplantation; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation
D051940:B7-2 Antigen; D019013:CD40 Antigens; C515371:Ccr7 protein, mouse; D016207:Cytokines; D054400:Receptors, CCR7; D019707:Receptors, Chemokine