Dynamics of CD11c(+) dendritic cell subsets in lymph nodes draining the site of intestinal nematode infection.
Helminth parasites drive dominant Th2 responses through an as yet unidentified pathway. We have previously shown that the rodent gastrointestinal nematode Nippostrongylus brasiliensis secretes products which selectively activate in vitro-derived dendritic cells to induce Th2 responses on in vivo transfer. We now show that, during active infection with this parasite, the draining mesenteric lymph node dendritic cell population is altered significantly. Although there is substantial expansion of DC numbers during infection, the CD86(hi)-CD8alpha(int)-CD11b(-) subset is markedly diminished, and expression levels of CD40, CD86 and CD103 are reduced. Notably, the reduced frequency of CD8alpha(int) DCs is evident only in those mesenteric lymph nodes draining the anterior site of infestation. In infections with the longer lived Heligmosomoides polygyrus, the proportion of CD8alpha(int) DCs in the MLNC falls to below 10% of total DC numbers by 35 days post-infection. Further, infection alters TLR responsiveness, as IL-12 production (as measured by ex vivo intracellular staining of CD11c(+) DCs) in response to LPS stimulation is reduced, while IL-6, TNF-alpha and in particular, IL-10 all increase following infection with either nematode parasite. These changes suggest the possibility that helminth parasites modulate gastrointestinal immunity both by inhibiting migration of CD8alpha(int) DCs to the draining lymph nodes, and modifying DC responsiveness in a manner which favours a Th2 outcome.
Balic
Adam
A
Institute of Immunology and Infection Research, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.
Smith
Katherine A
KA
Harcus
Yvonne
Y
Maizels
Rick M
RM
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D007411:Intestinal Diseases, Parasitic / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009351:Nematospiroides dubius / Q000276:immunology* / Q000472:pathogenicity; D009559:Nippostrongylus / Q000276:immunology* / Q000472:pathogenicity; D017206:Strongylida Infections / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology
D015703:Antigens, CD; D016207:Cytokines