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

• Published in: Frontiers in immunology Vol. 13; p. 877383
• Main Authors: Hernandez-Ramirez, Guadalupe, Pazos-Castro, Diego, Gonzalez-Klein, Zulema, Resuela-Gonzalez, Jose Luis, Fernandez-Bravo, Sergio, Palacio-Garcia, Lucia, Esteban, Vanesa, Garrido-Arandia, Maria, Tome-Amat, Jaime, Diaz-Perales, Araceli
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 30-06-2022
• Subjects: allergic asthma; Alt a 1; alveolar macrophage; Immunology; mouse model; TLR4
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.877383

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.