The common mouse protozoa Tritrichomonas muris alters mucosal T cell homeostasis and colitis susceptibility.
The mammalian gastrointestinal tract hosts a diverse community of microbes including bacteria, fungi, protozoa, helminths, and viruses. Through coevolution, mammals and these microbes have developed a symbiosis that is sustained through the host's continuous sensing of microbial factors and the generation of a tolerant or pro-inflammatory response. While analyzing T cell-driven colitis in nonlittermate mouse strains, we serendipitously identified that a nongenetic transmissible factor dramatically increased disease susceptibility. We identified the protozoan Tritrichomonas muris as the disease-exacerbating element. Furthermore, experimental colonization with T. muris induced an elevated Th1 response in the cecum of naive wild-type mice and accelerated colitis in Rag1-/-mice after T cell transfer. Overall, we describe a novel cross-kingdom interaction within the murine gut that alters immune cell homeostasis and disease susceptibility. This example of unpredicted microbial priming of the immune response highlights the importance of studying trans-kingdom interactions and serves as a stark reminder of the importance of using littermate controls in all mouse research.
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Nichole K
0000-0003-4037-1634
NK
Escalante
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Paul
P
Lemire
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Mayra
M
Cruz Tleugabulova
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
David
D
Prescott
Department of Oncological Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Arthur
A
Mortha
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Catherine J
CJ
Streutker
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Stephen E
SE
Girardin
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada dana.philpott@utoronto.ca.
Dana J
0000-0003-3238-6254
DJ
Philpott
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Thierry
0000-0001-8105-856X
T
Mallevaey
D000818:Animals; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D004198:Disease Susceptibility / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology*; D014318:Tritrichomonas / Q000276:immunology*
D018398:Homeodomain Proteins; C064658:RAG-1 protein