Presymptomatic differences in Toll-like receptor function in infants who have allergy
Presymptomatic differences in Toll-like receptor function in infants who have allergy
Background: Microbial exposure might play a key role in allergy development, but little is known about the role of Toll-like receptors (TLRs).
Objective: This study explored the association between neonatal TLR microbial recognition/function, allergy risk (maternal allergy), and prospective allergy development.
Methods: Cord blood mononuclear cells (n = 111) were cultured either alone or with optimal concentrations of TLR ligands: lipoteichoic acid (TLR2), polyinosinicpolycytidylic acid (TLR3), LPS with IFN-? (TLR4), flagellin (TLR5), imiquimod R837 (TLR7), or CpG (TLR9). Cytokine responses were assessed in relation to allergy risk (maternal allergy) and allergy outcomes (sensitization, food allergy, and atopic dermatitis) at 12 months of age.
Results: Maternal allergy (n = 59) was associated with significantly higher neonatal IL-12 and IFN-? responses to TLR2, TLR3, and TLR4 activation, whereas TNF-? and IL-6 responses to TLR2, TLR4, and TLR5 activation were significantly higher in newborns who subsequently had allergic disease (n = 32). Notably, consistent with previous reports, newborns who had disease had lower TH1 IFN-? response to mitogens (PHA).
Conclusion: Allergic disease was associated with increased (rather than decreased) perinatal TLR responses. Further studies are needed to determine how these responses track in the postnatal period and whether this relative hyperresponsiveness is a product of intrauterine influences, including maternal atopy, functional genetic polymorphisms, or both.
toll-like receptors, hygiene hypothesis, cord blood, allergic disease, cytokines, endotoxin
391-399.e5
Prescott, Susan
a81e2cd6-dafc-464b-9ed3-4a9a0e24bbb6
Noakes, Paul
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Chow, Bonita
3d4237b8-a944-4671-a578-2306db21c4ab
Breckler, Liza
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Thornton, Catherine
e91ddff8-1488-4930-a4db-48ce571e2ef8
Hollams, Elysia
66a9c95d-a883-4a1e-a387-5c3a20389b7b
Ali, May
de756e8b-f676-426a-a6c6-2d885a783145
van der Biggelaar, Anita
608d2225-a12d-4144-818c-3676e65b9369
Tulic, Meri
f4237d1d-fe22-4f2b-aae9-44600a4cf1ce
August 2008
Prescott, Susan
a81e2cd6-dafc-464b-9ed3-4a9a0e24bbb6
Noakes, Paul
0ed50cd9-de73-4851-8039-ee72860d8ae5
Chow, Bonita
3d4237b8-a944-4671-a578-2306db21c4ab
Breckler, Liza
35dff23d-b451-4232-9412-98c3e16df3ee
Thornton, Catherine
e91ddff8-1488-4930-a4db-48ce571e2ef8
Hollams, Elysia
66a9c95d-a883-4a1e-a387-5c3a20389b7b
Ali, May
de756e8b-f676-426a-a6c6-2d885a783145
van der Biggelaar, Anita
608d2225-a12d-4144-818c-3676e65b9369
Tulic, Meri
f4237d1d-fe22-4f2b-aae9-44600a4cf1ce
Prescott, Susan, Noakes, Paul, Chow, Bonita, Breckler, Liza, Thornton, Catherine, Hollams, Elysia, Ali, May, van der Biggelaar, Anita and Tulic, Meri
(2008)
Presymptomatic differences in Toll-like receptor function in infants who have allergy.
Journal of Allergy and Clinical Immunology, 122 (2), .
(doi:10.1016/j.jaci.2008.04.042).
(PMID:18571707)
Abstract
Background: Microbial exposure might play a key role in allergy development, but little is known about the role of Toll-like receptors (TLRs).
Objective: This study explored the association between neonatal TLR microbial recognition/function, allergy risk (maternal allergy), and prospective allergy development.
Methods: Cord blood mononuclear cells (n = 111) were cultured either alone or with optimal concentrations of TLR ligands: lipoteichoic acid (TLR2), polyinosinicpolycytidylic acid (TLR3), LPS with IFN-? (TLR4), flagellin (TLR5), imiquimod R837 (TLR7), or CpG (TLR9). Cytokine responses were assessed in relation to allergy risk (maternal allergy) and allergy outcomes (sensitization, food allergy, and atopic dermatitis) at 12 months of age.
Results: Maternal allergy (n = 59) was associated with significantly higher neonatal IL-12 and IFN-? responses to TLR2, TLR3, and TLR4 activation, whereas TNF-? and IL-6 responses to TLR2, TLR4, and TLR5 activation were significantly higher in newborns who subsequently had allergic disease (n = 32). Notably, consistent with previous reports, newborns who had disease had lower TH1 IFN-? response to mitogens (PHA).
Conclusion: Allergic disease was associated with increased (rather than decreased) perinatal TLR responses. Further studies are needed to determine how these responses track in the postnatal period and whether this relative hyperresponsiveness is a product of intrauterine influences, including maternal atopy, functional genetic polymorphisms, or both.
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Published date: August 2008
Keywords:
toll-like receptors, hygiene hypothesis, cord blood, allergic disease, cytokines, endotoxin
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Local EPrints ID: 180637
URI: http://eprints.soton.ac.uk/id/eprint/180637
ISSN: 0091-6749
PURE UUID: ec09570e-d642-4cca-84c6-20afa744d774
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Date deposited: 12 Apr 2011 13:19
Last modified: 15 Mar 2024 03:27
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Author:
Susan Prescott
Author:
Paul Noakes
Author:
Bonita Chow
Author:
Liza Breckler
Author:
Catherine Thornton
Author:
Elysia Hollams
Author:
May Ali
Author:
Anita van der Biggelaar
Author:
Meri Tulic
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