Graduate Student Penn State State College, Pennsylvania, United States
Disclosure(s):
Mengzhu Tang: No financial relationships to disclose
Introduction/Rationale: Respiratory infections caused by influenza viruses remain a global health burden, with disease severity in part determined by host immune responses. Immune cells have vitamin D receptors (VDR) and vitamin D has been shown to regulate host immunity to infection.
Methods: Wild-type (WT) and VDR knockout (KO) mice were infected with mouse-adapted influenza A/H1N1 (A/California/04/2009(H1N1pdm09)). Some WT mice also received exogenous PTH. Clinical scores and lung histology assessed disease severity, whereas viral load, immune cell responses, and cytokine levels in the lungs were quantified by viral titration assay, qPCR, ELISA, and flow cytometry.
Results: WT mice cleared virus efficiently with non-lethal disease, whereas VDR KO mice had 22% mortality, delayed viral clearance, and exacerbated lung pathology. These outcomes were accompanied by heightened type I and II interferon responses, increased infiltration of myeloid cells and CD4⁺ T cells but less natural killer (NK) cells into the lungs. Vitamin D deficiency and VDR KO result in very high parathyroid hormone (PTH) levels. WT mice were treated with PTH to determine the effects of PTH on host immunity to influenza virus infection. Influenza virus infection in PTH treated WT mice resulted in more severe clinical scores, higher viral burden, and amplified IFN-γ responses compared to WT mice.
Conclusion: Vitamin D deficiency and high PTH combine to create a hyperinflammatory environment with excessive interferon production, delayed viral clearance, and tissue injury. The work highlights a novel paradigm in which the vitamin D-PTH axis governs host resistance to influenza virus disease by controlling the amount of inflammation and the amount of virus in the lung. The data suggest that a low cost vitamin D supplement would improve vitamin D status, and limit PTH-driven immune dysregulation protecting the lung against influenza virus infection.
