ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1647780
This article is part of the Research TopicChemical Senses in Health and DiseaseView all 3 articles
Contribution of the Bitter Taste Signaling Pathway to Lung Inflammation During Staphylococcus Aureus-induced Pneumonia
Provisionally accepted
Liu Lingling1
Li Feng1*
Meng-Min Zhu1
Bo-Wen Niu1
Yu Huang1,2
Lixiang Chen1
Hua Yang1Boyin Qin1
Xiaohui Zhou1*- 1Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- 2Shanghai Normal University College of Life Sciences, Shanghai, China
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Bitter taste receptors (TAS2Rs), initially identified for chemosensory roles in the tongue, are expressed in extraoral tissues, including the airways. However, to date, it remains unclear whether bitter signaling is associated with susceptibility to bacterial infection in the lower airways and whether bitter signaling actually participates in the immune response in lung infection has yet to be genetically established. Here, we investigated the role of TAS2R signaling in Staphylococcus aureus-induced murine pneumonia via wild-type (WT) and several mutants (mTas2r104-/-/105-/-, mTas2r105-/-/114-/-, mTas2r104-/-/105-/-/114-/-, Gnat3-/- and Gnat3-/--mTas2r104-/-/105-/-) mice. Genetic disruption of TAS2Rs altered compensatory expression of other bitter receptors in the trachea and lungs, but did not affect immune cell composition in the lungs or thymus. Bitter receptor-deficient mice exhibited exacerbated pulmonary lesions at day 3 (D3) post-infection. Pulmonary infection significantly upregulated mTas2r105,106, 107, 108, 126, 136, 138 and Gnat3 in the lung. TAS2R signaling deficiency downregulated the expression of cytokines (e.g., IL-10, MIP-2) and antimicrobial peptides in the lungs and trachea, increased CD68+ macrophages in D3 lung tissues, amplified Ki67+ cell proliferation in alveolar and bronchiolar regions, and even impaired recovery from lung injury by day 14 (D14). Mechanistically, bitter taste pathway disruption dysregulated the mTOR pathway, reduced eNOS expression, and delayed resolution of pneumonia-induced injury. In summary, the current results collectively indicate that bitter taste signaling can modulate innate immune and inflammatory responses during S. aureus-induced lung infection.
Keywords: Bitter taste receptor, Staphylococcus aureus, Pneumonia, Inflammation, Cytokines
Received: 16 Jun 2025; Accepted: 24 Sep 2025.
Copyright: © 2025 Lingling, Feng, Zhu, Niu, Huang, Chen, Yang, Qin and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Li Feng, lifeng30286@shphc.org.cn
Xiaohui Zhou, zhouxiaohui@fudan.edu.cn
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