Microbial and maternal influences on allergic sensitization during childhood: defining a role for monocytes
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Allergic diseases are influenced by genetics and the environment. Maternal allergy appears to confer a higher risk for allergic sensitization than paternal allergy, suggesting an in utero influence. A decrease in particular infections or a lower exposure to microbial components during infancy is suggested to contribute to the high allergy prevalence in affluent societies. Toll-like receptors (TLR) 2 and 4 recognize peptidoglycan (PGN) and LPS respectively, are expressed on e.g. monocytes, and have been implicated in modulating the risk of IgE-sensitization. This thesis aimed to study the influence of maternal allergy and early microbial exposure on monocyte function and allergic sensitization during childhood.
Blood samples from children participating in a prospective allergy cohort were used. Two-year old infants with allergic mothers had lower IL-6 production and reduced activation of the TLR-signalling intermediate p38-MAPK in response to PGN than children with non-allergic mothers. In 5-year old children, allergic disease and not maternal allergy influenced monocytic TLR2-regulation. Five-year olds who were seropositive for Epstein-Barr virus (EBV) at 2-years of age had a lower risk of persistent IgE-sensitization while EBV contraction after 2-years of age related to a higher risk of IgE-sensitization. Upon in vitro stimulation, NK cells from EBV+ 2-year olds produced lower IFN-g levels. EBV+ 2-year olds had also lower systemic IFN-g. In comparison to CD14++CD16- monocytes, CD14+CD16+ cells induced NK-cell IFN-g more potently in vitro, and EBV+ infants tended to have lower proportions of these CD14+CD16+ monocytes.
This thesis highlights the importance of early-life microbial (EBV) exposure for a proper allergy-protective immunity. Also, maternal allergic heredity appears to influence monocytic microbial responses in early infancy. All these aspects relate to altered monocyte functionality, which suggest that they could have a role in allergic sensitization.
Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University , 2009. , 81 p.
Monocytes, allergic sensitization, maternal allergy, Toll-like receptor, p38-MAPK, IL-6, Epstein-Barr virus, early-life microbial exposure, NK cells, IFN-γ
Immunology in the medical area
Research subject Immunology
IdentifiersURN: urn:nbn:se:su:diva-27620ISBN: 978-91-7155-872-5OAI: oai:DiVA.org:su-27620DiVA: diva2:216587
2009-06-12, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 13:00 (English)
Prescott, Susan, Professor
Sverremark-Ekström, Eva, Associate professor
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