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Dynamics of CD11c+ dendritic cell subsets in lymph nodes draining the site of intestinal nematode infection

Balic, Adam, Smith, Katherine A., Harcus, Yvonne and Maizels, Rick M. 2009. Dynamics of CD11c+ dendritic cell subsets in lymph nodes draining the site of intestinal nematode infection. Immunology Letters 127 (1) , pp. 68-75. 10.1016/j.imlet.2009.09.001

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Abstract

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 CD86hi-CD8αint-CD11b− subset is markedly diminished, and expression levels of CD40, CD86 and CD103 are reduced. Notably, the reduced frequency of CD8αint 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 CD8αint 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-α 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 CD8αint DCs to the draining lymph nodes, and modifying DC responsiveness in a manner which favours a Th2 outcome.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QR Microbiology > QR180 Immunology
Uncontrolled Keywords: Cytokines; Helminth infection; Migration; Mucosal immunity
Publisher: Elsevier
ISSN: 0165-2478
Date of Acceptance: 8 September 2009
Last Modified: 18 Jan 2017 05:35
URI: http://orca.cf.ac.uk/id/eprint/91200

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