Vitamin A deficient mice exhibit increased viral antigens and enhanced cytokine/chemokine production in nasal tissues following respiratory virus infection despite the presence of FoxP3+ T cells.
The World Health Organization (WHO) estimates that 250 million children under the age of five suffer from vitamin A deficiencies (VAD). Individuals with VAD experience higher rates of mortality and increased morbidity during enteric and respiratory infections compared with those who are vitamin A sufficient. Previously, our laboratory has demonstrated that VAD mice have significantly impaired virus-specific IgA and CD8(+) T-cell responses in the airways. Here, we demonstrate that VAD mice experience enhanced cytokine/chemokine gene expression and release in the respiratory tract 10 days following virus infection compared with control vitamin A sufficient animals. Cytokines/chemokines that are reproducibly up-regulated at the gene expression and protein levels include IFNγ and IL-6. Despite previous indications that cytokine dysregulation in VAD animals might reflect low forkhead box P3 (FoxP3)-positive regulatory T-cell frequencies, we found no reduction in FoxP3(+) T cells in VAD respiratory tissues. As an alternative explanation for the high cytokine levels, we found that the extent of virus infection and the persistence of viral antigens were increased on day 10 post-infection in VAD animals compared with controls, and consequently that respiratory tract tissues had an increased potential to activate virus-specific T cells. Results encourage cautious management of viral infections in patients with VAD, as efforts to enhance FoxP3(+) T cell frequencies and quell immune effectors could potentially exacerbate disease if the virus has not been cleared.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Rhiannon R
RR
Penkert
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Sherri L
SL
Surman
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Bart G
BG
Jones
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Robert E
RE
Sealy
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Peter
P
Vogel
Hartwell Center, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Geoffrey
G
Neale
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA julia.hurwitz@stjude.org.
Julia L
JL
Hurwitz
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism*; D004035:Diet Therapy; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009666:Nose / Q000276:immunology* / Q000821:virology; D011247:Pregnancy; D010253:Respirovirus Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D029082:Sendai virus / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D015854:Up-Regulation; D019562:Viral Load; D014801:Vitamin A / Q000008:administration & dosage* / Q000097:blood; D014802:Vitamin A Deficiency / Q000150:complications / Q000276:immunology* / Q000821:virology
D000956:Antigens, Viral; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015850:Interleukin-6; D014801:Vitamin A; D007371:Interferon-gamma
Treg; cytokine; parainfluenza virus; respiratory tract; vitamin A deficiency