Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells

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dc.contributor.authorCook, Peter Cen_ZA
dc.contributor.authorAynsley, Sarah Aen_ZA
dc.contributor.authorTurner, Joseph Den_ZA
dc.contributor.authorJenkins, Gavin Ren_ZA
dc.contributor.authorVan Rooijen, Nicoen_ZA
dc.contributor.authorLeeto, Mosiuoaen_ZA
dc.contributor.authorBrombacher, Franken_ZA
dc.contributor.authorMountford, Adrian Pen_ZA
dc.date.accessioned2016-01-11T06:53:29Z
dc.date.available2016-01-11T06:53:29Z
dc.date.issued2011en_ZA
dc.description.abstractInfection of the mammalian host by schistosome larvae occurs via the skin, although nothing is known about the development of immune responses to multiple exposures of schistosome larvae, and/or their excretory/secretory (E/S) products. Here, we show that multiple (4x) exposures, prior to the onset of egg laying by adult worms, modulate the skin immune response and induce CD4+ cell hypo-responsiveness in the draining lymph node, and even modulate the formation of hepatic egg-induced granulomas. Compared to mice exposed to a single infection (1x), dermal cells from multiply infected mice (4x), were less able to support lymph node cell proliferation. Analysis of dermal cells showed that the most abundant in 4x mice were eosinophils (F4/80+MHC-II−), but they did not impact the ability of antigen presenting cells (APC) to support lymphocyte proliferation to parasite antigen in vitro. However, two other cell populations from the dermal site of infection appear to have a critical role. The first comprises arginase-1+, Ym-1+ alternatively activated macrophage-like cells, and the second are functionally compromised MHC-IIhi cells. Through the administration of exogenous IL-12 to multiply infected mice, we show that these suppressive myeloid cell phenotypes form as a consequence of events in the skin, most notably an enrichment of IL-4 and IL-13, likely resulting from an influx of RELMα-expressing eosinophils. We further illustrate that the development of these suppressive dermal cells is dependent upon IL-4Rα signalling. The development of immune hypo-responsiveness to schistosome larvae and their effect on the subsequent response to the immunopathogenic egg is important in appreciating how immune responses to helminth infections are modulated by repeated exposure to the infective early stages of development.en_ZA
dc.identifier.apacitationCook, P. C., Aynsley, S. A., Turner, J. D., Jenkins, G. R., Van Rooijen, N., Leeto, M., ... Mountford, A. P. (2011). Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells. <i>PLoS One</i>, http://hdl.handle.net/11427/16279en_ZA
dc.identifier.chicagocitationCook, Peter C, Sarah A Aynsley, Joseph D Turner, Gavin R Jenkins, Nico Van Rooijen, Mosiuoa Leeto, Frank Brombacher, and Adrian P Mountford "Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells." <i>PLoS One</i> (2011) http://hdl.handle.net/11427/16279en_ZA
dc.identifier.citationCook, P. C., Aynsley, S. A., Turner, J. D., Jenkins, G. R., Van Rooijen, N., Leeto, M., ... & Mountford, A. P. (2011). Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells. PLoS Pathog, 7(3), e1001323. doi:10.1371/journal.ppat.1001323en_ZA
dc.identifier.ris TY - Journal Article AU - Cook, Peter C AU - Aynsley, Sarah A AU - Turner, Joseph D AU - Jenkins, Gavin R AU - Van Rooijen, Nico AU - Leeto, Mosiuoa AU - Brombacher, Frank AU - Mountford, Adrian P AB - Infection of the mammalian host by schistosome larvae occurs via the skin, although nothing is known about the development of immune responses to multiple exposures of schistosome larvae, and/or their excretory/secretory (E/S) products. Here, we show that multiple (4x) exposures, prior to the onset of egg laying by adult worms, modulate the skin immune response and induce CD4+ cell hypo-responsiveness in the draining lymph node, and even modulate the formation of hepatic egg-induced granulomas. Compared to mice exposed to a single infection (1x), dermal cells from multiply infected mice (4x), were less able to support lymph node cell proliferation. Analysis of dermal cells showed that the most abundant in 4x mice were eosinophils (F4/80+MHC-II−), but they did not impact the ability of antigen presenting cells (APC) to support lymphocyte proliferation to parasite antigen in vitro. However, two other cell populations from the dermal site of infection appear to have a critical role. The first comprises arginase-1+, Ym-1+ alternatively activated macrophage-like cells, and the second are functionally compromised MHC-IIhi cells. Through the administration of exogenous IL-12 to multiply infected mice, we show that these suppressive myeloid cell phenotypes form as a consequence of events in the skin, most notably an enrichment of IL-4 and IL-13, likely resulting from an influx of RELMα-expressing eosinophils. We further illustrate that the development of these suppressive dermal cells is dependent upon IL-4Rα signalling. The development of immune hypo-responsiveness to schistosome larvae and their effect on the subsequent response to the immunopathogenic egg is important in appreciating how immune responses to helminth infections are modulated by repeated exposure to the infective early stages of development. DA - 2011 DB - OpenUCT DO - 10.1371/journal.ppat.1001323 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells TI - Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells UR - http://hdl.handle.net/11427/16279 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16279
dc.identifier.urihttp://dx.doi.org/10.1371/journal.ppat.1001323
dc.identifier.vancouvercitationCook PC, Aynsley SA, Turner JD, Jenkins GR, Van Rooijen N, Leeto M, et al. Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells. PLoS One. 2011; http://hdl.handle.net/11427/16279.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2011 Cook et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plospathogensen_ZA
dc.subject.otherSkin infectionsen_ZA
dc.subject.otherEosinophilsen_ZA
dc.subject.otherImmune responseen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherSchistosomaen_ZA
dc.subject.otherLarvaeen_ZA
dc.subject.otherLymphocytesen_ZA
dc.subject.otherAntigen-presenting cellsen_ZA
dc.titleMultiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cellsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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