A gut commensal protozoan determines respiratory disease outcomes by shaping pulmonary immunity

  • Cell. 2025 Jan 23;188(2):316-330.e12. doi: 10.1016/j.cell.2024.11.020.
Kyle Burrows  1 ,  Louis Ngai  1 ,  Pailin Chiaranunt  1 ,  Jacqueline Watt  2 ,  Sarah Popple  3 ,  Brian Forde  4 ,  Saven Denha  5 ,  Vitoria M Olyntho  5 ,  Siu Ling Tai  1 ,  Eric Yixiao Cao  1 ,  Susana Tejeda-Garibay  6 ,  Joshua F E Koenig  5 ,  Katrin D Mayer-Barber  7 ,  Catherine J Streutker  8 ,  Katrina K Hoyer  6 ,  Lisa C Osborne  3 ,  Jun Liu  2 ,  Liam O'Mahony  9 ,  Arthur Mortha  10
Affiliations
  • 1. Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • 2. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
  • 3. Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
  • 4. School of Microbiology, University College Cork, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • 5. Schroeder Allergy and Immunology Research Institute, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
  • 6. Health Sciences Research Institute, University of California Merced, Merced, CA, USA.
  • 7. Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA.
  • 8. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
  • 9. Department of Medicine, University College Cork, Cork, Ireland.
  • 10. Department of Immunology, University of Toronto, Toronto, ON, Canada. Electronic address: [email protected].
PMID: 39706191 DOI: 10.1016/j.cell.2024.11.020
Abstract

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.

Keywords
Mycobacterium tuberculosis; Tritrichomonas musculis; asthma; eosinophils; group 2 innate lymphoid cells; gut-lung axis; interorgan lymphocyte trafficking; microbiome; protozoan commensal.