Consequences of Vitamin A Deficiency: Immunoglobulin Dysregulation, Squamous Cell Metaplasia, Infectious Disease, and Death
Vitamin A is an important regulator of immune protection, but it is often overlooked in studies of infectious disease. Vitamin A binds an array of nuclear receptors (e.g., retinoic acid receptor, peroxisome proliferator-activated receptor, retinoid X receptor) and influences the barrier and immune c...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/15/5570 |
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| author | Sherri L. Surman Rhiannon R. Penkert Robert E. Sealy Bart G. Jones Tony N. Marion Peter Vogel Julia L. Hurwitz |
| author_facet | Sherri L. Surman Rhiannon R. Penkert Robert E. Sealy Bart G. Jones Tony N. Marion Peter Vogel Julia L. Hurwitz |
| author_sort | Sherri L. Surman |
| collection | DOAJ |
| description | Vitamin A is an important regulator of immune protection, but it is often overlooked in studies of infectious disease. Vitamin A binds an array of nuclear receptors (e.g., retinoic acid receptor, peroxisome proliferator-activated receptor, retinoid X receptor) and influences the barrier and immune cells responsible for pathogen control. Children and adults in developed and developing countries are often vitamin A-deficient or insufficient, characteristics associated with poor health outcomes. To gain a better understanding of the protective mechanisms influenced by vitamin A, we examined immune factors and epithelial barriers in vitamin A deficient (VAD) mice, vitamin D deficient (VDD) mice, double deficient (VAD+VDD) mice, and mice on a vitamin-replete diet (controls). Some mice received insults, including intraperitoneal injections with complete and incomplete Freund’s adjuvant (emulsified with PBS alone or with DNA + Fus-1 peptide) or intranasal inoculations with Sendai virus (SeV). Both before and after insults, the VAD and VAD+VDD mice exhibited abnormal serum immunoglobulin isotypes (e.g., elevated IgG2b levels, particularly in males) and cytokine/chemokine patterns (e.g., elevated eotaxin). Even without insult, when the VAD and VAD+VDD mice reached 3–6 months of age, they frequently exhibited opportunistic ascending bacterial urinary tract infections. There were high frequencies of nephropathy (squamous cell hyperplasia of the renal urothelium, renal scarring, and ascending pyelonephritis) and death in the VAD and VAD+VDD mice. When younger VAD mice were infected with SeV, the predominant lesion was squamous cell metaplasia of respiratory epithelium in lungs and bronchioles. Results highlight a critical role for vitamin A in the maintenance of healthy immune responses, epithelial cell integrity, and pathogen control. |
| first_indexed | 2024-03-10T17:59:14Z |
| format | Article |
| id | doaj.art-4c620bedcb1f4ec0b104821fcdb25599 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T17:59:14Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4c620bedcb1f4ec0b104821fcdb255992023-11-20T09:00:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012115557010.3390/ijms21155570Consequences of Vitamin A Deficiency: Immunoglobulin Dysregulation, Squamous Cell Metaplasia, Infectious Disease, and DeathSherri L. Surman0Rhiannon R. Penkert1Robert E. Sealy2Bart G. Jones3Tony N. Marion4Peter Vogel5Julia L. Hurwitz6Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USAVitamin A is an important regulator of immune protection, but it is often overlooked in studies of infectious disease. Vitamin A binds an array of nuclear receptors (e.g., retinoic acid receptor, peroxisome proliferator-activated receptor, retinoid X receptor) and influences the barrier and immune cells responsible for pathogen control. Children and adults in developed and developing countries are often vitamin A-deficient or insufficient, characteristics associated with poor health outcomes. To gain a better understanding of the protective mechanisms influenced by vitamin A, we examined immune factors and epithelial barriers in vitamin A deficient (VAD) mice, vitamin D deficient (VDD) mice, double deficient (VAD+VDD) mice, and mice on a vitamin-replete diet (controls). Some mice received insults, including intraperitoneal injections with complete and incomplete Freund’s adjuvant (emulsified with PBS alone or with DNA + Fus-1 peptide) or intranasal inoculations with Sendai virus (SeV). Both before and after insults, the VAD and VAD+VDD mice exhibited abnormal serum immunoglobulin isotypes (e.g., elevated IgG2b levels, particularly in males) and cytokine/chemokine patterns (e.g., elevated eotaxin). Even without insult, when the VAD and VAD+VDD mice reached 3–6 months of age, they frequently exhibited opportunistic ascending bacterial urinary tract infections. There were high frequencies of nephropathy (squamous cell hyperplasia of the renal urothelium, renal scarring, and ascending pyelonephritis) and death in the VAD and VAD+VDD mice. When younger VAD mice were infected with SeV, the predominant lesion was squamous cell metaplasia of respiratory epithelium in lungs and bronchioles. Results highlight a critical role for vitamin A in the maintenance of healthy immune responses, epithelial cell integrity, and pathogen control.https://www.mdpi.com/1422-0067/21/15/5570vitamin A deficiencysquamous cell metaplasiaabnormal cytokinesabnormal immunoglobulinsinfections |
| spellingShingle | Sherri L. Surman Rhiannon R. Penkert Robert E. Sealy Bart G. Jones Tony N. Marion Peter Vogel Julia L. Hurwitz Consequences of Vitamin A Deficiency: Immunoglobulin Dysregulation, Squamous Cell Metaplasia, Infectious Disease, and Death International Journal of Molecular Sciences vitamin A deficiency squamous cell metaplasia abnormal cytokines abnormal immunoglobulins infections |
| title | Consequences of Vitamin A Deficiency: Immunoglobulin Dysregulation, Squamous Cell Metaplasia, Infectious Disease, and Death |
| title_full | Consequences of Vitamin A Deficiency: Immunoglobulin Dysregulation, Squamous Cell Metaplasia, Infectious Disease, and Death |
| title_fullStr | Consequences of Vitamin A Deficiency: Immunoglobulin Dysregulation, Squamous Cell Metaplasia, Infectious Disease, and Death |
| title_full_unstemmed | Consequences of Vitamin A Deficiency: Immunoglobulin Dysregulation, Squamous Cell Metaplasia, Infectious Disease, and Death |
| title_short | Consequences of Vitamin A Deficiency: Immunoglobulin Dysregulation, Squamous Cell Metaplasia, Infectious Disease, and Death |
| title_sort | consequences of vitamin a deficiency immunoglobulin dysregulation squamous cell metaplasia infectious disease and death |
| topic | vitamin A deficiency squamous cell metaplasia abnormal cytokines abnormal immunoglobulins infections |
| url | https://www.mdpi.com/1422-0067/21/15/5570 |
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