Burrows Kyle, Ngai Louis, Chiaranunt Pailin, Watt Jacqueline, Popple Sarah, Forde Brian, Denha Saven, Olyntho Vitoria M, Tai Siu Ling, Cao Eric Yixiao, Tejeda-Garibay Susana, Koenig Joshua F E, Mayer-Barber Katrin D, Streutker Catherine J, Hoyer Katrina K, Osborne Lisa C, Liu Jun, O'Mahony Liam, Mortha Arthur
Department of Immunology, University of Toronto, Toronto, ON, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Cell. 2025 Jan 23;188(2):316-330.e12. doi: 10.1016/j.cell.2024.11.020. Epub 2024 Dec 19.
The underlying mechanisms used by the intestinal microbiota to shape disease outcomes of the host are poorly understood. Here, we show that the gut commensal protozoan, Tritrichomonas musculis (T.mu), remotely shapes the lung immune landscape to facilitate perivascular shielding of the airways by eosinophils. Lung-specific eosinophilia requires a tripartite immune network between gut-derived inflammatory group 2 innate lymphoid cells and lung-resident T cells and B cells. This network exacerbates the severity of allergic airway inflammation while hindering the systemic dissemination of pulmonary Mycobacterium tuberculosis. The identification of protozoan DNA sequences in the sputum of patients with severe allergic asthma further emphasizes the relevance of commensal protozoa in human disease. Collectively, these findings demonstrate that a commensal protozoan tunes pulmonary immunity via a gut-operated lung immune network, promoting both beneficial and detrimental disease outcomes in response to environmental airway allergens and pulmonary infections.
肠道微生物群影响宿主疾病结局的潜在机制目前仍知之甚少。在此，我们表明肠道共生原生动物——肌肉三毛滴虫（T.mu），可远程塑造肺部免疫格局，以促进嗜酸性粒细胞对气道的血管周围保护。肺部特异性嗜酸性粒细胞增多需要肠道来源的2型炎症性固有淋巴细胞与肺部驻留的T细胞和B细胞之间形成三方免疫网络。该网络会加剧过敏性气道炎症的严重程度，同时阻碍肺部结核分枝杆菌的全身扩散。在重度过敏性哮喘患者痰液中发现原生动物DNA序列，进一步凸显了共生原生动物在人类疾病中的相关性。总体而言，这些发现表明，一种共生原生动物通过肠道调控的肺部免疫网络调节肺部免疫，在应对环境气道过敏原和肺部感染时，既促进有益的疾病结局，也促进有害的疾病结局。
