Postdoctoral Scholar Ohio State Univ. Col. of Vet. Med. Columbus, Ohio, United States
Disclosure(s):
Marisa Joldrichsen, PhD: No financial relationships to disclose
Introduction/Rationale:
Introduction: The extreme variability of infection severity between SARS-CoV-2 patients suggests that complex mechanisms regulate host responses to this respiratory pathogen. We addressed the role of the intestinal epithelium in host susceptibility and responses to SARS-CoV-2 and focused on Paneth cells. These cells of the small intestine are specialized in the production of antimicrobials, and their dysfunction is often associated with inflammatory bowel diseases.
Methods:
Methods: Wild-type C57BL/6 and Paneth cell KO mice of both sexes were infected with the mouse-adapted SARS-CoV-2 MA10. Body weight, body temperature, and behavior were monitored to assess the severity of diseases. Early host responses to infection were determined by flow cytometry analysis of peripheral blood leukocyte subsets, viral load in lung tissues and the profile of host mRNA responses. We also quantified anti-SARS-Cov-2 antibody responses in the bloodstream and mucosal tissues.
Results:
Results: Loss of Paneth cells in the Paneth cell KO mice is associated with a dysbiosis broadly characterized by significant decrease in the amount of Bacteroidota. The profile of innate immune cells was also altered in the gut and lungs of Paneth cell KO mice. In response to SARS-CoV-2 infection, Paneth cell KO mice developed an early increase in the number of blood neutrophils, eosinophils, non-classical monocytes, T cells and B cells compared to the wild-type mice. In contrast, the early blood response of control wild-type mice was characterized by a significant increase in the number of monocytes, specifically classical monocytes. The profile of host mRNA responses 3 days post infection and the magnitude and profile of systemic and mucosal anti-SARS-Cov-2 antibody further confirmed the influence of Paneth cells on the outcome of SARS-CoV-2 infection.
Conclusion: These findings highlight the importance of gastrointestinal health in shaping innate immune cells in the airways and host response to respiratory viruses.
