Mice Expressing Cosegregating Single Nucleotide Polymorphisms (D298G and N397I) in TLR4 Have Enhanced Responses to House Dust Mite Allergen.

Autor:	Fink MY; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD.; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD., Qi X; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD., Shirey KA; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD., Fanaroff R; Department of Anatomical Pathology, University of Maryland Medical Center, Baltimore, MD., Chapoval S; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD.; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD., Viscardi RM; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD; and., Vogel SN; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD., Keegan AD; Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD; akeegan@som.umaryland.edu.; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD.; Maryland Health Care System, Baltimore VA Medical Center, Baltimore, MD.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2022 May 01; Vol. 208 (9), pp. 2085-2097. Date of Electronic Publication: 2022 Apr 08.
DOI:	10.4049/jimmunol.2100926
Abstrakt:	Asthma is a common and ubiquitous chronic respiratory disease that is associated with airway inflammation and hyperreactivity resulting in airway obstruction. It is now accepted that asthma is controlled by a combination of host genetics and environment in a rather complex fashion; however, the link between sensing of the environment and development and exacerbation of allergic lung inflammation is unclear. Human populations expressing cosegregating D299G and T399I polymorphisms in the TLR4 gene are associated with a decreased risk for asthma in adults along with hyporesponsiveness to inhaled LPS, the TLR4 ligand. However, these data do not account for other human genetic or environmental factors. Using a novel mouse strain that expresses homologous human TLR4 polymorphisms (TLR4-single nucleotide polymorphism [SNP]), we directly tested the effect of these TLR4 polymorphisms on in vivo responses to allergens using two models of induction. We report that intact TLR4 is required for allergic inflammation when using the OVA and LPS model of induction, as cellular and pathological benchmarks were diminished in both TLR4-SNP and TLR4-deficent mice. However, in the more clinically relevant model using house dust mite extract for induction, responses were enhanced in the TLR4-SNP mice, as evidenced by greater levels of eosinophilic inflammation, Th2 cytokine production, and house dust mite-specific IgG1 production compared with wild-type mice; however, mucus production and airway hyperreactivity were not affected. These results suggest that the TLR4 polymorphic variants (genes) interact differently with the allergic stimulation (environment). (Copyright © 2022 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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