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Chronic helminth infection promotes immune regulation in vivo through dominance of CD11cloCD103- Dendritic cells

Smith, Katherine A., Hochweller, K., Hammerling, G. J., Boon, L., MacDonald, A. S. and Maizels, R. M. 2011. Chronic helminth infection promotes immune regulation in vivo through dominance of CD11cloCD103- Dendritic cells. The Journal of Immunology 186 (12) , pp. 7098-7109. 10.4049/jimmunol.1003636

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Abstract

Gastrointestinal helminth infections are extremely prevalent in many human populations and are associated with downmodulated immune responsiveness. In the experimental model system of Heligmosomoides polygyrus, a chronic infection establishes in mice, accompanied by a modulated Th2 response and increased regulatory T cell (Treg) activity. To determine if dendritic cell (DC) populations in the lymph nodes draining the intestine are responsible for the regulatory effects of chronic infection, we first identified a population of CD11clo nonplasmacytoid DCs that expand after chronic H. polygyrus infection. The CD11clo DCs are underrepresented in magnetic bead-sorted preparations and spared from deletion in CD11c-diptheria toxin receptor mice. After infection, CD11clo DCs did not express CD8, CD103, PDCA, or Siglec-H and were poorly responsive to TLR stimuli. In DC/T cell cocultures, CD11clo DCs from naive and H. polygyrus-infected mice could process and present protein Ag, but induced lower levels of Ag-specific CD4+ T cell proliferation and effector cytokine production, and generated higher percentages of Foxp3+ T cells in the presence of TGF-β. Treg generation was also dependent on retinoic acid receptor signaling. In vivo, depletion of CD11chi DCs further favored the dominance of the CD11clo DC phenotype. After CD11chi DC depletion, effector responses were inhibited dramatically, but the expansion in Treg numbers after H. polygyrus infection was barely compromised, showing a significantly higher regulatory/effector CD4+ T cell ratio compared with that of CD11chi DC-intact animals. Thus, the proregulatory environment of chronic intestinal helminth infection is associated with the in vivo predominance of a newly defined phenotype of CD11clo tolerogenic DCs.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QR Microbiology > QR180 Immunology
Publisher: American Association of Immunologists
ISSN: 0022-1767
Date of Acceptance: 3 April 2011
Last Modified: 18 Jan 2017 05:35
URI: http://orca.cf.ac.uk/id/eprint/91198

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