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Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny.

MK Tulic, M Hodder, al A Forsberg et, S McCarthy, T Richman, N D'Vaz, AH van den Biggelaar, CA Thornton, SL Prescott, Cathy Thornton Orcid Logo

Journal of Allergy and Clinical Immunology, Volume: 127, Issue: 2, Pages: 470 - 478

Swansea University Author: Cathy Thornton Orcid Logo

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DOI (Published version): 10.1016/j.jaci.2010.09.020

Abstract

BACKGROUND: Microbial products are of central interest in the modulation of allergic propensity.OBJECTIVE: We sought to explore whether allergic children show differences in microbial Toll-like receptor (TLR)-mediated responses over their first 5 years of life.METHODS: Mononuclear cells isolated fro...

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Published in: Journal of Allergy and Clinical Immunology
ISSN: 00916749
Published: Elsevier 2011
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URI: https://cronfa.swan.ac.uk/Record/cronfa9992
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fullrecord <?xml version="1.0"?><rfc1807><datestamp>2013-11-08T11:15:12.0176836</datestamp><bib-version>v2</bib-version><id>9992</id><entry>2012-03-21</entry><title>Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny.</title><swanseaauthors><author><sid>c71a7a4be7361094d046d312202bce0c</sid><ORCID>0000-0002-5153-573X</ORCID><firstname>Cathy</firstname><surname>Thornton</surname><name>Cathy Thornton</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2012-03-21</date><deptcode>BMS</deptcode><abstract>BACKGROUND: Microbial products are of central interest in the modulation of allergic propensity.OBJECTIVE: We sought to explore whether allergic children show differences in microbial Toll-like receptor (TLR)-mediated responses over their first 5 years of life.METHODS: Mononuclear cells isolated from 35 allergic and 35 nonallergic children at birth and 1, 2.5, and 5 years of age were stimulated with TLR2-TLR9 ligands to study innate immune function and with allergens or mitogen to assess adaptive T-cell responses. Cytokine production was measured by using Luminex multiplexing technology.RESULTS: Nonallergic children show progressive and significant age-related increases in innate cytokine responses (IL-1&#x3B2;, IL-6, TNF-&#x3B1;, and IL-10) to virtually all TLR ligands. This innate maturation corresponds with a parallel increase in adaptive T(H)1 (IFN-&#x3B3;) responses to allergens and mitogens. In contrast, allergic children show exaggerated innate responses at birth (P &amp;#60; .01) but a relative decrease with age thereafter, so that by age 5 years, TLR responses are attenuated compared with those seen in nonallergic subjects (P &amp;#60; .05). This early hyperresponsiveness in allergic subjects fails to translate to a corresponding maturation of T(H)1 function, which remains attenuated relative to that seen in nonallergic subjects but is associated with a characteristic age-dependent increase in allergen-specific T(H)2 responses (P &amp;#60; .01).CONCLUSION: Our findings suggest significant differences in the developmental trajectory of innate immune function in children with allergic disease that might contribute to the recognized differences in postnatal adaptive T-cell immunity</abstract><type>Journal Article</type><journal>Journal of Allergy and Clinical Immunology</journal><volume>127</volume><journalNumber>2</journalNumber><paginationStart>470</paginationStart><paginationEnd>478</paginationEnd><publisher>Elsevier</publisher><issnPrint>00916749</issnPrint><issnElectronic/><keywords>allergy; immunity; early life; toll like receptors</keywords><publishedDay>31</publishedDay><publishedMonth>12</publishedMonth><publishedYear>2011</publishedYear><publishedDate>2011-12-31</publishedDate><doi>10.1016/j.jaci.2010.09.020</doi><url>www.jacionline.org/article/S0091-6749(10)01487-9/abstract</url><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm/><lastEdited>2013-11-08T11:15:12.0176836</lastEdited><Created>2012-03-21T16:17:15.0000000</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>MK</firstname><surname>Tulic</surname><order>1</order></author><author><firstname>M</firstname><surname>Hodder</surname><order>2</order></author><author><firstname>al</firstname><surname>A Forsberg et</surname><order>3</order></author><author><firstname>S</firstname><surname>McCarthy</surname><order>4</order></author><author><firstname>T</firstname><surname>Richman</surname><order>5</order></author><author><firstname>N</firstname><surname>D'Vaz</surname><order>6</order></author><author><firstname>AH van den</firstname><surname>Biggelaar</surname><order>7</order></author><author><firstname>CA</firstname><surname>Thornton</surname><order>8</order></author><author><firstname>SL</firstname><surname>Prescott</surname><order>9</order></author><author><firstname>Cathy</firstname><surname>Thornton</surname><orcid>0000-0002-5153-573X</orcid><order>10</order></author></authors><documents/><OutputDurs/></rfc1807>
spelling 2013-11-08T11:15:12.0176836 v2 9992 2012-03-21 Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny. c71a7a4be7361094d046d312202bce0c 0000-0002-5153-573X Cathy Thornton Cathy Thornton true false 2012-03-21 BMS BACKGROUND: Microbial products are of central interest in the modulation of allergic propensity.OBJECTIVE: We sought to explore whether allergic children show differences in microbial Toll-like receptor (TLR)-mediated responses over their first 5 years of life.METHODS: Mononuclear cells isolated from 35 allergic and 35 nonallergic children at birth and 1, 2.5, and 5 years of age were stimulated with TLR2-TLR9 ligands to study innate immune function and with allergens or mitogen to assess adaptive T-cell responses. Cytokine production was measured by using Luminex multiplexing technology.RESULTS: Nonallergic children show progressive and significant age-related increases in innate cytokine responses (IL-1β, IL-6, TNF-α, and IL-10) to virtually all TLR ligands. This innate maturation corresponds with a parallel increase in adaptive T(H)1 (IFN-γ) responses to allergens and mitogens. In contrast, allergic children show exaggerated innate responses at birth (P &#60; .01) but a relative decrease with age thereafter, so that by age 5 years, TLR responses are attenuated compared with those seen in nonallergic subjects (P &#60; .05). This early hyperresponsiveness in allergic subjects fails to translate to a corresponding maturation of T(H)1 function, which remains attenuated relative to that seen in nonallergic subjects but is associated with a characteristic age-dependent increase in allergen-specific T(H)2 responses (P &#60; .01).CONCLUSION: Our findings suggest significant differences in the developmental trajectory of innate immune function in children with allergic disease that might contribute to the recognized differences in postnatal adaptive T-cell immunity Journal Article Journal of Allergy and Clinical Immunology 127 2 470 478 Elsevier 00916749 allergy; immunity; early life; toll like receptors 31 12 2011 2011-12-31 10.1016/j.jaci.2010.09.020 www.jacionline.org/article/S0091-6749(10)01487-9/abstract COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2013-11-08T11:15:12.0176836 2012-03-21T16:17:15.0000000 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine MK Tulic 1 M Hodder 2 al A Forsberg et 3 S McCarthy 4 T Richman 5 N D'Vaz 6 AH van den Biggelaar 7 CA Thornton 8 SL Prescott 9 Cathy Thornton 0000-0002-5153-573X 10
title Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny.
spellingShingle Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny.
Cathy Thornton
title_short Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny.
title_full Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny.
title_fullStr Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny.
title_full_unstemmed Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny.
title_sort Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny.
author_id_str_mv c71a7a4be7361094d046d312202bce0c
author_id_fullname_str_mv c71a7a4be7361094d046d312202bce0c_***_Cathy Thornton
author Cathy Thornton
author2 MK Tulic
M Hodder
al A Forsberg et
S McCarthy
T Richman
N D'Vaz
AH van den Biggelaar
CA Thornton
SL Prescott
Cathy Thornton
format Journal article
container_title Journal of Allergy and Clinical Immunology
container_volume 127
container_issue 2
container_start_page 470
publishDate 2011
institution Swansea University
issn 00916749
doi_str_mv 10.1016/j.jaci.2010.09.020
publisher Elsevier
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
url www.jacionline.org/article/S0091-6749(10)01487-9/abstract
document_store_str 0
active_str 0
description BACKGROUND: Microbial products are of central interest in the modulation of allergic propensity.OBJECTIVE: We sought to explore whether allergic children show differences in microbial Toll-like receptor (TLR)-mediated responses over their first 5 years of life.METHODS: Mononuclear cells isolated from 35 allergic and 35 nonallergic children at birth and 1, 2.5, and 5 years of age were stimulated with TLR2-TLR9 ligands to study innate immune function and with allergens or mitogen to assess adaptive T-cell responses. Cytokine production was measured by using Luminex multiplexing technology.RESULTS: Nonallergic children show progressive and significant age-related increases in innate cytokine responses (IL-1β, IL-6, TNF-α, and IL-10) to virtually all TLR ligands. This innate maturation corresponds with a parallel increase in adaptive T(H)1 (IFN-γ) responses to allergens and mitogens. In contrast, allergic children show exaggerated innate responses at birth (P &#60; .01) but a relative decrease with age thereafter, so that by age 5 years, TLR responses are attenuated compared with those seen in nonallergic subjects (P &#60; .05). This early hyperresponsiveness in allergic subjects fails to translate to a corresponding maturation of T(H)1 function, which remains attenuated relative to that seen in nonallergic subjects but is associated with a characteristic age-dependent increase in allergen-specific T(H)2 responses (P &#60; .01).CONCLUSION: Our findings suggest significant differences in the developmental trajectory of innate immune function in children with allergic disease that might contribute to the recognized differences in postnatal adaptive T-cell immunity
published_date 2011-12-31T03:11:28Z
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