Myeloid cell expression of the VDR and parathyroid hormone control the host response to influenza infection in mice
- 1Department of Veterinary and Biomedical Sciences, The Pennsylvania State University , , ,
- 2Department of Kinesiology, The Pennsylvania State University , , ,
Abstract
Introduction: Respiratory infections caused by seasonal influenza viruses remain a major global health burden. Vitamin D receptor (VDR) signaling regulates immune responses, but the role of the VDR and its interaction with parathyroid hormone (PTH) in host resistance to H1N1 influenza infection is not understood.
Methods: Global VDR knockout (KO) mice, or myeloid (M) deletion of the VDR (M-VDR KO) and the respective wildtype (WT) littermates were infected with H1N1 influenza virus. Additional experiments treated WT mice with intermittent PTH or vehicle and then infected them with a H1N1 influenza A virus. Disease severity, mortality, viral burden and clearance, lung pathology, and inflammatory cytokine responses were evaluated.
Results: H1N1 influenza infection of WT mice resulted in non-lethal disease, whereas VDR KO mice had 21% mortality, delayed viral clearance, more severe symptoms and lung pathology. The increased severity of respiratory disease was accompanied by higher type I and II interferon responses in the lungs. M-VDR KO mice had increased disease severity and delayed viral clearance compared to WT littermates. PTH-treated WT mice had increased clinical scores, influenza M gene, and cytokine responses compared to vehicle treated WT mice.
Discussion: The work describes 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. In addition, the data suggest that VDR expression in myeloid cells is critical for controlling the early innate immune response to influenza viruses.
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BibTeX
@article{tang2026myeloid,
title = {{Myeloid cell expression of the VDR and parathyroid hormone control the host response to influenza infection in mice}},
author = {Mengzhu Tang and Nicole E. Froelich and Nicholas J. Hanna and Veronika C. Weaver and Gustavo A. Nader and Troy C. Sutton and Margherita T. Cantorna},
journal = {Frontiers in immunology},
year = {2026},
month = sep,
doi = {10.3389/fimmu.2026.1939052},
url = {https://europepmc.org/article/PMC/PMC13661438},
note = {CC BY},
}
RIS
TY - JOUR
TI - Myeloid cell expression of the VDR and parathyroid hormone control the host response to influenza infection in mice
AU - Mengzhu Tang
AU - Nicole E. Froelich
AU - Nicholas J. Hanna
AU - Veronika C. Weaver
AU - Gustavo A. Nader
AU - Troy C. Sutton
AU - Margherita T. Cantorna
PY - 2026
DA - 2026/09/30
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1939052
UR - https://europepmc.org/article/PMC/PMC13661438
AB - Introduction: Respiratory infections caused by seasonal influenza viruses remain a major global health burden. Vitamin D receptor (VDR) signaling regulates immune responses, but the role of the VDR and its interaction with parathyroid hormone (PTH) in host resistance to H1N1 influenza infection is not understood. Methods: Global VDR knockout (KO) mice, or myeloid (M) deletion of the VDR (M-VDR KO) and the respective wildtype (WT) littermates were infected with H1N1 influenza virus. Additional experiments treated WT mice with intermittent PTH or vehicle and then infected them with a H1N1 influenza A virus. Disease severity, mortality, viral burden and clearance, lung pathology, and inflammatory cytokine responses were evaluated. Results: H1N1 influenza infection of WT mice resulted in non-lethal disease, whereas VDR KO mice had 21% mortality, delayed viral clearance, more severe symptoms and lung pathology. The increased severity of respiratory disease was accompanied by higher type I and II interferon responses in the lungs. M-VDR KO mice had increased disease severity and delayed viral clearance compared to WT littermates. PTH-treated WT mice had increased clinical scores, influenza M gene, and cytokine responses compared to vehicle treated WT mice. Discussion: The work describes 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. In addition, the data suggest that VDR expression in myeloid cells is critical for controlling the early innate immune response to influenza viruses.
SN - 1664-3224
ER -