Frontiers in Immunology (Jun 2022)

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

  • 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

DOI
https://doi.org/10.3389/fimmu.2022.877383
Journal volume & issue
Vol. 13

Abstract

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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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