Mast cells augment adaptive immunity by orchestrating dendritic cell trafficking through infected tissues.
Mast cells (MCs) are best known for eliciting harmful reactions, mostly after primary immunity has been established. Here, we report that, during footpad infection with E. coli in MC-deficient mice, as compared to their MC-sufficient counterparts, the serum antibody response is significantly diminished and less protective following passive immunization in a urinary tract infection (UTI) model in wild-type mice. MCs were found to recruit large numbers of dendritic cells (DCs) into the infected tissue site, which eventually migrated into draining lymph nodes (DLNs) during a prolonged time course. This pattern of trafficking was facilitated by MC-generated TNF, which increased the expression of E-selectin on local blood vessels. Antibody blockade of E-selectin inhibited DC recruitment into the site of infection and DLNs and consequently impaired the primary humoral immune response. Thus, during infection, resident MCs contribute to the primary protective adaptive response through recruitment of DCs from the circulation into infected sites.
Shelburne
Christopher P
CP
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. cps4@duke.edu
Nakano
Hideki
H
St John
Ashley L
AL
Chan
Cheryl
C
McLachlan
James B
JB
Gunn
Michael D
MD
Staats
Herman F
HF
Abraham
Soman N
SN
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D019040:E-Selectin / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology*; D005260:Female; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018461:Soft Tissue Infections / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014552:Urinary Tract Infections / Q000276:immunology
D000907:Antibodies, Bacterial; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha