title: Differential expression of cytokines in response to respiratory syncytial virus infection of calves with high or low circulating 25-hydroxyvitamin D3.
abstract: Deficiency of serum levels of 25-hydroxyvitamin D(3) has been related to increased risk of lower respiratory tract infections in children. Respiratory syncytial virus (RSV) is a leading cause of low respiratory tract infections in infants and young children. The neonatal calf model of RSV infection shares many features in common with RSV infection in infants and children. In the present study, we hypothesized that calves with low circulating levels of 25-hydroxyvitamin D(3) (25(OH)D(3)) would be more susceptible to RSV infection than calves with high circulating levels of 25(OH)D(3). Calves were fed milk replacer diets with different levels of vitamin D for a 10 wk period to establish two treatment groups, one with high (177 ng/ml) and one with low (32.5 ng/ml) circulating 25(OH)D(3). Animals were experimentally infected via aerosol challenge with RSV. Data on circulating 25(OH)D(3) levels showed that high and low concentrations of 25(OH)D(3) were maintained during infection. At necropsy, lung lesions due to RSV were similar in the two vitamin D treatment groups. We show for the first time that RSV infection activates the vitamin D intracrine pathway in the inflamed lung. Importantly, however, we observed that cytokines frequently inhibited by this pathway in vitro are, in fact, either significantly upregulated (IL-12p40) or unaffected (IFN-γ) in the lungs of RSV-infected calves with high circulating levels of 25(OH)D(3). Our data indicate that while vitamin D does have an immunomodulatory role during RSV infection, there was no significant impact on pathogenesis during the early phases of RSV infection. Further examination of the potential effects of vitamin D status on RSV disease resolution will require longer-term studies with immunologically sufficient and deficient vitamin D levels.
authors.affiliation: Ruminant Diseases and Immunology Research Unit, National Animal Disease Center, United States Department of Agriculture, Agricultural Research Service, Ames, Iowa, United States of America. randy.sacco@ars.usda.gov
authors.forename: Randy E
authors.initials: RE
authors.lastname: Sacco
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nonnecke
authors.forename: Mitchell V
authors.initials: MV
authors.lastname: Palmer
authors.forename: W Ray
authors.initials: WR
authors.lastname: Waters
authors.forename: John D
authors.initials: JD
authors.lastname: Lippolis
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Reinhardt
mesh_terms: D000818:Animals; D002112:Calcifediol / Q000097:blood*; D002118:Calcium / Q000097:blood; D002417:Cattle; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000821:virology; D018167:Receptors, Calcitriol / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D018112:Respiratory Syncytial Virus, Bovine / Q000276:immunology / Q000302:isolation & purification; D013250:Steroid Hydroxylases / Q000235:genetics; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D018167:Receptors, Calcitriol; D050826:Suppressor of Cytokine Signaling Proteins; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002112:Calcifediol; D002118:Calcium