Aspiration of acidified milk induces milk allergy by activating alveolar macrophages in mice
Background: Epidemiological studies have identified associations between gastroesophageal reflux (GER) and cow's milk allergy (CMA) in infants. However, the role of GER in the development of CMA remains poorly understood. Our primary objectives were to develop a mouse model that suggests GER as...
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Elsevier
2025-01-01
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| Series: | Allergology International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1323893024000820 |
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| author | Akiko Nakaoka Takayasu Nomura Atsushi Suzuki Kazuyoshi Ozeki Hirohito Kita Shinji Saitoh |
| author_facet | Akiko Nakaoka Takayasu Nomura Atsushi Suzuki Kazuyoshi Ozeki Hirohito Kita Shinji Saitoh |
| author_sort | Akiko Nakaoka |
| collection | DOAJ |
| description | Background: Epidemiological studies have identified associations between gastroesophageal reflux (GER) and cow's milk allergy (CMA) in infants. However, the role of GER in the development of CMA remains poorly understood. Our primary objectives were to develop a mouse model that suggests GER as a potential pathogenic mechanism for CMA and to elucidate the immunological mechanisms that connect lung innate immunity with CMA. Methods: Mice were exposed to cow's milk (CM) treated with hydrochloric acid through repeated aspiration into their airways. Subsequently, they were challenged by intraperitoneal injection of CM extract. The immunological mechanisms were investigated using comprehensive single-cell RNA sequencing (scRNA-seq) analysis of the lungs, combined with the use of genetically modified mice. Results: Mice exposed to CM mixed with hydrochloric acid via airway sensitization developed CMA, as evidenced by the production of antigen-specific IgE and IgG antibodies, and the induction of anaphylaxis upon systemic antigen administration. In contrast, aspiration of CM alone did not induce CMA. scRNA-seq analysis revealed potential roles of alveolar macrophages in response to hydrochloric acid. Mice lacking the TLR4 pathway were protected from developing CMA. Conclusions: We have developed a novel mouse model for CMA that utilizes the natural antigen and follows the physiological airway sensitization pathway, thus potentially resembling clinical scenarios. This model, named the acidified milk aspiration-induced allergy model, has the potential to shed light on the role of early innate immunity by analyzing a more physiological model. |
| format | Article |
| id | doaj-art-d066ddbf4b4c4f7d881abc008f89e20e |
| institution | Kabale University |
| issn | 1323-8930 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Allergology International |
| spelling | doaj-art-d066ddbf4b4c4f7d881abc008f89e20e2025-01-04T04:56:05ZengElsevierAllergology International1323-89302025-01-0174197104Aspiration of acidified milk induces milk allergy by activating alveolar macrophages in miceAkiko Nakaoka0Takayasu Nomura1Atsushi Suzuki2Kazuyoshi Ozeki3Hirohito Kita4Shinji Saitoh5Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanDepartment of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Corresponding author. Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan.Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanDepartment of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanDepartment of Immunology, Mayo Clinic Rochester, Rochester, MN, and Mayo Clinic Arizona, Scottsdale, AZ, USADepartment of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanBackground: Epidemiological studies have identified associations between gastroesophageal reflux (GER) and cow's milk allergy (CMA) in infants. However, the role of GER in the development of CMA remains poorly understood. Our primary objectives were to develop a mouse model that suggests GER as a potential pathogenic mechanism for CMA and to elucidate the immunological mechanisms that connect lung innate immunity with CMA. Methods: Mice were exposed to cow's milk (CM) treated with hydrochloric acid through repeated aspiration into their airways. Subsequently, they were challenged by intraperitoneal injection of CM extract. The immunological mechanisms were investigated using comprehensive single-cell RNA sequencing (scRNA-seq) analysis of the lungs, combined with the use of genetically modified mice. Results: Mice exposed to CM mixed with hydrochloric acid via airway sensitization developed CMA, as evidenced by the production of antigen-specific IgE and IgG antibodies, and the induction of anaphylaxis upon systemic antigen administration. In contrast, aspiration of CM alone did not induce CMA. scRNA-seq analysis revealed potential roles of alveolar macrophages in response to hydrochloric acid. Mice lacking the TLR4 pathway were protected from developing CMA. Conclusions: We have developed a novel mouse model for CMA that utilizes the natural antigen and follows the physiological airway sensitization pathway, thus potentially resembling clinical scenarios. This model, named the acidified milk aspiration-induced allergy model, has the potential to shed light on the role of early innate immunity by analyzing a more physiological model.http://www.sciencedirect.com/science/article/pii/S1323893024000820Airway sensitizationCow's milk allergyGastroesophageal refluxInnate immunityToll-like receptor 4 |
| spellingShingle | Akiko Nakaoka Takayasu Nomura Atsushi Suzuki Kazuyoshi Ozeki Hirohito Kita Shinji Saitoh Aspiration of acidified milk induces milk allergy by activating alveolar macrophages in mice Allergology International Airway sensitization Cow's milk allergy Gastroesophageal reflux Innate immunity Toll-like receptor 4 |
| title | Aspiration of acidified milk induces milk allergy by activating alveolar macrophages in mice |
| title_full | Aspiration of acidified milk induces milk allergy by activating alveolar macrophages in mice |
| title_fullStr | Aspiration of acidified milk induces milk allergy by activating alveolar macrophages in mice |
| title_full_unstemmed | Aspiration of acidified milk induces milk allergy by activating alveolar macrophages in mice |
| title_short | Aspiration of acidified milk induces milk allergy by activating alveolar macrophages in mice |
| title_sort | aspiration of acidified milk induces milk allergy by activating alveolar macrophages in mice |
| topic | Airway sensitization Cow's milk allergy Gastroesophageal reflux Innate immunity Toll-like receptor 4 |
| url | http://www.sciencedirect.com/science/article/pii/S1323893024000820 |
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