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

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Peter C Cook, Sarah A Aynsley, Joseph D Turner, Gavin R Jenkins, Nico Van Rooijen, Mosiuoa Leeto, Frank Brombacher, Adrian P Mountford
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/029cab324ffe43299c6dab7fc3ada1a1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:029cab324ffe43299c6dab7fc3ada1a1
record_format	dspace
spelling	oai:doaj.org-article:029cab324ffe43299c6dab7fc3ada1a12021-11-18T06:03:31ZMultiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.1553-73661553-737410.1371/journal.ppat.1001323https://doaj.org/article/029cab324ffe43299c6dab7fc3ada1a12011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21445234/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Infection 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-II(hi) 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.Peter C CookSarah A AynsleyJoseph D TurnerGavin R JenkinsNico Van RooijenMosiuoa LeetoFrank BrombacherAdrian P MountfordPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 3, p e1001323 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Peter C Cook Sarah A Aynsley Joseph D Turner Gavin R Jenkins Nico Van Rooijen Mosiuoa Leeto Frank Brombacher Adrian P Mountford Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.
description	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-II(hi) 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.
format	article
author	Peter C Cook Sarah A Aynsley Joseph D Turner Gavin R Jenkins Nico Van Rooijen Mosiuoa Leeto Frank Brombacher Adrian P Mountford
author_facet	Peter C Cook Sarah A Aynsley Joseph D Turner Gavin R Jenkins Nico Van Rooijen Mosiuoa Leeto Frank Brombacher Adrian P Mountford
author_sort	Peter C Cook
title	Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.
title_short	Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.
title_full	Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.
title_fullStr	Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.
title_full_unstemmed	Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.
title_sort	multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by th2 conditioning of dermal myeloid cells.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/029cab324ffe43299c6dab7fc3ada1a1
work_keys_str_mv	AT peterccook multiplehelminthinfectionoftheskincauseslymphocytehyporesponsivenessmediatedbyth2conditioningofdermalmyeloidcells AT sarahaaynsley multiplehelminthinfectionoftheskincauseslymphocytehyporesponsivenessmediatedbyth2conditioningofdermalmyeloidcells AT josephdturner multiplehelminthinfectionoftheskincauseslymphocytehyporesponsivenessmediatedbyth2conditioningofdermalmyeloidcells AT gavinrjenkins multiplehelminthinfectionoftheskincauseslymphocytehyporesponsivenessmediatedbyth2conditioningofdermalmyeloidcells AT nicovanrooijen multiplehelminthinfectionoftheskincauseslymphocytehyporesponsivenessmediatedbyth2conditioningofdermalmyeloidcells AT mosiuoaleeto multiplehelminthinfectionoftheskincauseslymphocytehyporesponsivenessmediatedbyth2conditioningofdermalmyeloidcells AT frankbrombacher multiplehelminthinfectionoftheskincauseslymphocytehyporesponsivenessmediatedbyth2conditioningofdermalmyeloidcells AT adrianpmountford multiplehelminthinfectionoftheskincauseslymphocytehyporesponsivenessmediatedbyth2conditioningofdermalmyeloidcells
_version_	1718424644335173632

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

Ejemplares similares