Maternal allergy modulates cord blood hematopoietic progenitor Toll-like receptor expression and function

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• 作者：Pia Reece BSc^a ; Amudhinie Thanendran BSc^a ; Lynn Crawford BSc^a ; Meri K. Tulic PhD^b ; Lehana Thabane PhD^d ; ^e ; Susan L. Prescott PhD ; MD^b ; Roma Sehmi PhD^c ; Judah A. Denburg MD^a ; ^{denburg@mcmaster.ca}
• 关键词：Atopy ; Toll-like receptors ; cytokine receptors ; cord blood ; CD34 ; eosinophil-basophil
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2011
• 出版时间：February 2011
• 年：2011
• 卷：127
• 期：2
• 页码：447-453
• 全文大小：348 K

文摘

Background

Little is known regarding the prenatal determinants of innate immune responses in relation to infant allergic risk. Environmental exposures, including microbial stimuli, might predispose susceptible subjects to atopy and asthma in early infancy or even in utero.

Objective

Because Toll-like receptors (TLRs) recognize microbial products and because cord blood (CB) progenitor alterations have been observed in neonates at risk for atopy, we investigated the expression and function of TLRs on CB hematopoietic progenitors in relation to atopic risk, as defined by maternal allergic sensitization.

Methods

Thirty-two (15 with low and 17 with high atopic risk) infant CB samples were assessed for phenotypic and functional alterations in CD34⁺ cells by means of flow cytometry and methylcellulose culture, respectively. CD34⁺ hematopoietic progenitors were stained for TLR-2, TLR-4, TLR-9, GM-CSF receptor α, IL-5 receptor α, and IL-3 receptor α or cultured in methylcellulose assays for hematopoietic cytokine-stimulated eosinophil-basophil (Eo/B) colony-forming units (CFUs) with or without LPS.

Results

High-atopic-risk infants had significantly lower CB CD34⁺ cell TLR-2, TLR-4, and TLR-9 expression (P = .009). High-risk infant progenitors gave rise to significantly more Eo/B CFUs (P = .002) with hematopoietic cytokine (IL-3, IL-5, or GM-CSF) stimulation ex vivo. Although LPS costimulation induced Eo/B CFUs from both low- and high-risk infant CB CD34⁺ cells, this response was significantly (P = .020) muted in the high-risk CB progenitors.

Conclusions

Neonatal CB CD34⁺ hematopoietic progenitor cell TLR expression and functional responsiveness are altered in CB from atopic at-risk infants. Maternal allergic sensitization might modulate hematopoietic progenitor TLR expression and function in utero; specifically, Eo/B “lineage priming” at birth might be circumvented through engagement of TLR pathways in early life.