Repository logo
 

THE ROLE OF TOLL-LIKE RECEPTOR 2 IN MODULATION OF BREAST MILK COMPONENTS AND ORAL TOLERANCE

dc.contributor.authorDawod, Bassel
dc.contributor.copyright-releaseYesen_US
dc.contributor.degreeDoctor of Philosophyen_US
dc.contributor.departmentDepartment of Pathologyen_US
dc.contributor.ethics-approvalReceiveden_US
dc.contributor.external-examinerDr. Kirsi M. Jarvinen-Seppoen_US
dc.contributor.graduate-coordinatorDr. Paola Marcatoen_US
dc.contributor.manuscriptsYesen_US
dc.contributor.thesis-readerDr. David Hoskinen_US
dc.contributor.thesis-readerDr. Andrew Stadnyken_US
dc.contributor.thesis-readerDr. Thomas Arnasonen_US
dc.contributor.thesis-supervisorDr. Jean S. Marshallen_US
dc.date.accessioned2021-03-11T17:09:00Z
dc.date.available2021-03-11T17:09:00Z
dc.date.defence2021-01-13
dc.date.issued2021-03-11T17:09:00Z
dc.description.abstractFood allergy is a common immune-mediated disease of early life that has increased in incidence over the past three decades. The immaturity of the neonatal immune system makes them prone to the development of allergy. Dietary components are essential for their immune responses to develop normal oral tolerance. A diversity of scientific opinions about breast milk's ability to protect against the development of food allergies might be related to dramatic variations in milk-associated immune mediators (IMs) between mothers. Pattern recognition receptors (PRRs) are one of the multiple components that regulate IM production. Toll-like receptor 2 (TLR2), a PRR that is highly expressed in the mammary gland and immune cells, mediates secretion of both pro and anti-inflammatory IMs, some of which are found in breast milk. The role of maternal TLR2 in regulating breast milk components and infant immune system development is still unknown. We evaluated the impact of maternal TLR2 deficiency in susceptibility to allergic diseases in infants using a cross-fostering model in mice. Milk from TLR2 deficient dams had altered IMs content compared to WT dams’ milk. It failed to induce optimal gastrointestinal integrity and expansion of oral tolerance essential immune cells, including tolerogenic dendritic cells (DCs) and regulatory T cells (Tregs) in pups, thus increasing their susceptibility food sensitization. In humans, a soluble form of TLR2 (sTLR2) was detectable in breast milk, in variable amounts, generally higher than those observed in cow’s milk and baby formulas. sTLR2 was undetectable in mouse milk. Human milk sTLR2 concentrations were lower in homozygous mothers with specific single nucleotide polymorphisms (SNPs) in the TLR2 gene and higher in food allergic mothers. We found that a high level of sTLR2 in milk was associated with an increased incidence of allergies in infants if they were breastfed exclusively for six months regardless of the maternal allergic status. Collectively, our findings and experimental models demonstrate significant associations between maternal TLR2 and food allergy development in infants and the importance of considering both maternal genetic factors and feeding practices.en_US
dc.identifier.urihttp://hdl.handle.net/10222/80295
dc.language.isoenen_US
dc.subjectFood allergyen_US
dc.subjectBreastfeedingen_US
dc.subjecthuman milken_US
dc.subjectoral toleranceen_US
dc.subjectallergyen_US
dc.subjectbreast milken_US
dc.subjectTLR2en_US
dc.subjectSNPen_US
dc.titleTHE ROLE OF TOLL-LIKE RECEPTOR 2 IN MODULATION OF BREAST MILK COMPONENTS AND ORAL TOLERANCEen_US
dc.typeThesisen_US

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
BasselDawod2021.pdf
Size:
7.38 MB
Format:
Adobe Portable Document Format
Description:
PhD thesis

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description: