Protein Malnutrition Alters Tryptophan and Angiotensin-Converting Enzyme 2 Homeostasis and Adaptive Immune Responses in Human Rotavirus-Infected Gnotobiotic Pigs with Human Infant Fecal Microbiota Transplant

• Published in: Clinical and vaccine immunology Vol. 24; no. 8
• Main Authors: Fischer, David D., Kandasamy, Sukumar, Paim, Francine C., Langel, Stephanie N., Alhamo, Moyasar A., Shao, Lulu, Chepngeno, Juliet, Miyazaki, Ayako, Huang, Huang-Chi, Kumar, Anand, Rajashekara, Gireesh, Saif, Linda J., Vlasova, Anastasia N.
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.08.2017
• Subjects: Adaptive Immunity; Animals; B-Lymphocytes - immunology; Clinical Immunology; Diarrhea - virology; Fecal Microbiota Transplantation; Germ-Free Life; Homeostasis; Humans; Immunoglobulin A - immunology; Infant; Microbiota; Peptidyl-Dipeptidase A - blood; Peptidyl-Dipeptidase A - metabolism; Protein Deficiency - complications; Rotavirus - immunology; Rotavirus - isolation & purification; Rotavirus - physiology; Rotavirus Infections - complications; Rotavirus Infections - immunology; Rotavirus Infections - metabolism; Sus scrofa; T-Lymphocytes - immunology; Tryptophan - blood; Tryptophan - metabolism; gnotobiotic; ACE2; fecal microbiota; malnutrition; rotavirus; tryptophan
• ISSN: 1556-6811; 1556-679X; 1556-679X
• DOI: 10.1128/CVI.00172-17

Malnutrition leads to increased morbidity and is evident in almost half of all deaths in children under the age of 5 years. Mortality due to rotavirus diarrhea is common in developing countries where malnutrition is prevalent; however, the relationship between malnutrition and rotavirus infection remains unclear. In this study, gnotobiotic pigs transplanted with the fecal microbiota of a healthy 2-month-old infant were fed protein-sufficient or -deficient diets and infected with virulent human rotavirus (HRV). After human rotavirus infection, protein-deficient pigs had decreased human rotavirus antibody titers and total IgA concentrations, systemic T helper (CD3 + CD4 + ) and cytotoxic T (CD3 + CD8 + ) lymphocyte frequencies, and serum tryptophan and angiotensin I-converting enzyme 2. Additionally, deficient-diet pigs had impaired tryptophan catabolism postinfection compared with sufficient-diet pigs. Tryptophan supplementation was tested as an intervention in additional groups of fecal microbiota-transplanted, rotavirus-infected, sufficient- and deficient-diet pigs. Tryptophan supplementation increased the frequencies of regulatory (CD4 + or CD8 + CD25 + FoxP3 + ) T cells in pigs on both the sufficient and the deficient diets. These results suggest that a protein-deficient diet impairs activation of the adaptive immune response following HRV infection and alters tryptophan homeostasis.