Effect of Vitamin A Deficiency in Dysregulating Immune Responses to Influenza Virus and Increasing Mortality Rates After Bacterial Coinfections. (22nd September 2020)

• Record Type: Journal Article
• Authors: Penkert, Rhiannon R; Smith, Amanda P; Hrincius, Eike R; McCullers, Jonathan A; Vogel, Peter; Smith, Amber M; Hurwitz, Julia L
• Is Part Of: Journal of infectious diseases. Volume 223:Number 10(2021)
• Page Start: 1806
• Page End: 1816
• Publication Date: 2020-09-22
• Subjects: respiratory virus -- coinfections -- host response; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiaa597
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: Secondary bacterial coinfections are ranked as a leading cause of hospitalization and morbid conditions associated with influenza. Because vitamin A deficiency (VAD) and insufficiency are frequent in both developed and developing countries, we asked how VAD influences coinfection severity. Methods: VAD and control mice were infected with influenza virus for evaluation of inflammatory cytokines, cellular immune responses, and viral clearance. Influenza-infected mice were coinfected with Streptococcus pneumoniae to study weight loss and survival. Results: Naive VAD mouse lungs exhibited dysregulated immune function. Neutrophils were enhanced in frequency and there was a significant reduction in RANTES (regulated on activation of normal T cells expressed and secreted), a chemokine instrumental in T-cell homing and recruitment. After influenza virus infection, VAD mice experienced failures in CD4 + T-cell recruitment and B-cell organization into lymphoid structures in the lung. VAD mice exhibited higher viral titers than controls and slow viral clearance. There were elevated levels of inflammatory cytokines and innate cell subsets in the lungs. However, arginase, a marker of alternatively activated M2 macrophages, was rare. When influenza-infected VAD animals were exposed to bacteria, they experienced a 100% mortality rate. Conclusion: Data showed that VAD dysregulated the immune response. Consequently, secondary bacterial infections were 100% lethal in influenza-infected VAD mice. Abstract : Vitamin A–deficient (VAD) mice exhibited dysregulated immune function. After influenza virus infection, compared with controls, they had relatively few CD4 + T cells, arginase-positive cells, and organized lymphoid structures in lungs. Secondary bacterial infections were 100% lethal in VAD mice.