Alt a 1 Promotes Allergic Asthma In Vivo Through TLR4-Alveolar Macrophages

The mold Alternaria alternata is one of the main sources of asthma exacerbation, being its major allergen, Alt a 1, indispensable for its development. The main objective of this work was to answer two main questions: 1) can Alt a 1 by itself (without any other context) induce an asthmatic profile in...

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Main Authors: Guadalupe Hernandez-Ramirez, Diego Pazos-Castro, Zulema Gonzalez-Klein, Jose Luis Resuela-Gonzalez, Sergio Fernandez-Bravo, Lucia Palacio-Garcia, Vanesa Esteban, Maria Garrido-Arandia, Jaime Tome-Amat, Araceli Diaz-Perales
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.877383/full
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author Guadalupe Hernandez-Ramirez
Diego Pazos-Castro
Diego Pazos-Castro
Zulema Gonzalez-Klein
Zulema Gonzalez-Klein
Jose Luis Resuela-Gonzalez
Sergio Fernandez-Bravo
Lucia Palacio-Garcia
Vanesa Esteban
Maria Garrido-Arandia
Maria Garrido-Arandia
Jaime Tome-Amat
Araceli Diaz-Perales
Araceli Diaz-Perales
author_facet Guadalupe Hernandez-Ramirez
Diego Pazos-Castro
Diego Pazos-Castro
Zulema Gonzalez-Klein
Zulema Gonzalez-Klein
Jose Luis Resuela-Gonzalez
Sergio Fernandez-Bravo
Lucia Palacio-Garcia
Vanesa Esteban
Maria Garrido-Arandia
Maria Garrido-Arandia
Jaime Tome-Amat
Araceli Diaz-Perales
Araceli Diaz-Perales
author_sort Guadalupe Hernandez-Ramirez
collection DOAJ
description The mold Alternaria alternata is one of the main sources of asthma exacerbation, being its major allergen, Alt a 1, indispensable for its development. The main objective of this work was to answer two main questions: 1) can Alt a 1 by itself (without any other context) induce an asthmatic profile in vivo?; and 2) Which molecular mechanisms take place during this phenomenon? To answer both questions, we have developed a mouse model of allergic asthma using only Alt a 1 for mice sensitization. We also made use of in-vitro cellular models and computational studies to support some aspects of our hypothesis. Our results showed that Alt a 1 can induce an asthmatic phenotype, promoting tissue remodeling and infiltration of CD45+ cells, especially eosinophils and macrophages (Siglec F+ and F4/80+). Also, we have found that Alt a 1 sensitization is mediated by the TLR4-macrophage axis.
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spelling doaj.art-6ec1b4f30ba447a3956e36249081be152022-12-22T00:22:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.877383877383Alt a 1 Promotes Allergic Asthma In Vivo Through TLR4-Alveolar MacrophagesGuadalupe Hernandez-Ramirez0Diego Pazos-Castro1Diego Pazos-Castro2Zulema Gonzalez-Klein3Zulema Gonzalez-Klein4Jose Luis Resuela-Gonzalez5Sergio Fernandez-Bravo6Lucia Palacio-Garcia7Vanesa Esteban8Maria Garrido-Arandia9Maria Garrido-Arandia10Jaime Tome-Amat11Araceli Diaz-Perales12Araceli Diaz-Perales13Centre for Plant Biotechnology and Genomics Universidad Politécnica de Madrid, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Cientificas (UPM –INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainCentre for Plant Biotechnology and Genomics Universidad Politécnica de Madrid, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Cientificas (UPM –INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainDepartment of Biotechnology-Plant Biology, Escuela Tecnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas (ETSIAAB), Universidad Politécnica de Madrid, Madrid, SpainCentre for Plant Biotechnology and Genomics Universidad Politécnica de Madrid, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Cientificas (UPM –INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainDepartment of Biotechnology-Plant Biology, Escuela Tecnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas (ETSIAAB), Universidad Politécnica de Madrid, Madrid, SpainCentre for Plant Biotechnology and Genomics Universidad Politécnica de Madrid, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Cientificas (UPM –INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainDepartment of Allergy and Immunology, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid (UAM), Madrid, SpainDepartment of Allergy and Immunology, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid (UAM), Madrid, SpainDepartment of Allergy and Immunology, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid (UAM), Madrid, SpainCentre for Plant Biotechnology and Genomics Universidad Politécnica de Madrid, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Cientificas (UPM –INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainDepartment of Biotechnology-Plant Biology, Escuela Tecnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas (ETSIAAB), Universidad Politécnica de Madrid, Madrid, SpainCentre for Plant Biotechnology and Genomics Universidad Politécnica de Madrid, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Cientificas (UPM –INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainCentre for Plant Biotechnology and Genomics Universidad Politécnica de Madrid, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Cientificas (UPM –INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainDepartment of Biotechnology-Plant Biology, Escuela Tecnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas (ETSIAAB), Universidad Politécnica de Madrid, Madrid, SpainThe mold Alternaria alternata is one of the main sources of asthma exacerbation, being its major allergen, Alt a 1, indispensable for its development. The main objective of this work was to answer two main questions: 1) can Alt a 1 by itself (without any other context) induce an asthmatic profile in vivo?; and 2) Which molecular mechanisms take place during this phenomenon? To answer both questions, we have developed a mouse model of allergic asthma using only Alt a 1 for mice sensitization. We also made use of in-vitro cellular models and computational studies to support some aspects of our hypothesis. Our results showed that Alt a 1 can induce an asthmatic phenotype, promoting tissue remodeling and infiltration of CD45+ cells, especially eosinophils and macrophages (Siglec F+ and F4/80+). Also, we have found that Alt a 1 sensitization is mediated by the TLR4-macrophage axis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.877383/fullallergic asthmaAlt a 1TLR4alveolar macrophagemouse model
spellingShingle Guadalupe Hernandez-Ramirez
Diego Pazos-Castro
Diego Pazos-Castro
Zulema Gonzalez-Klein
Zulema Gonzalez-Klein
Jose Luis Resuela-Gonzalez
Sergio Fernandez-Bravo
Lucia Palacio-Garcia
Vanesa Esteban
Maria Garrido-Arandia
Maria Garrido-Arandia
Jaime Tome-Amat
Araceli Diaz-Perales
Araceli Diaz-Perales
Alt a 1 Promotes Allergic Asthma In Vivo Through TLR4-Alveolar Macrophages
Frontiers in Immunology
allergic asthma
Alt a 1
TLR4
alveolar macrophage
mouse model
title Alt a 1 Promotes Allergic Asthma In Vivo Through TLR4-Alveolar Macrophages
title_full Alt a 1 Promotes Allergic Asthma In Vivo Through TLR4-Alveolar Macrophages
title_fullStr Alt a 1 Promotes Allergic Asthma In Vivo Through TLR4-Alveolar Macrophages
title_full_unstemmed Alt a 1 Promotes Allergic Asthma In Vivo Through TLR4-Alveolar Macrophages
title_short Alt a 1 Promotes Allergic Asthma In Vivo Through TLR4-Alveolar Macrophages
title_sort alt a 1 promotes allergic asthma in vivo through tlr4 alveolar macrophages
topic allergic asthma
Alt a 1
TLR4
alveolar macrophage
mouse model
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.877383/full
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