Elevated non-specific immunity and normal Listeria clearance in young and old vitamin D receptor knockout mice.
1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and the vitamin D receptor (VDR) are important regulators of autoimmunity. The effect of the VDR on the ability of mice to fight a primary or secondary infection has not been determined. Young and old VDR knockout (KO) mice were able to clear both primary and secondary infections with Listeria monocytogenes. However, the kinetics of clearance was somewhat delayed in the absence of the VDR. Memory T cell development was not different in young VDR KO and wild-type (WT) mice; however, old VDR KO mice had significantly less memory T cells than their WT counterparts but still mounted an adequate immune response as determined by the complete clearance of L. monocytogenes. Although the primary and secondary immune responses were largely intact in the VDR KO mice, the old VDR KO mice had increased cytokines and antibody responses compared with the old WT mice. In particular, old VDR KO mice had elevated antigen non-specific antibodies; however, these magnified immune responses did not correspond to more effective Listeria clearance. The increased antibody and cytokine responses in the old VDR KO mice are consistent with the increased susceptibility of these mice to autoimmunity.
Bruce
Danny
D
Department of Veterinary and Biomedical Science, Center for Immunology and Infectious Disease, Pennsylvania State University, University Park, PA 16802, USA.
Whitcomb
James P
JP
August
Avery
A
McDowell
Mary Ann
MA
Cantorna
Margherita T
MT
D000375:Aging / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D002117:Calcitriol / Q000276:immunology; D002469:Cell Separation; D015169:Colony Count, Microbial; D000939:Epitopes / Q000097:blood / Q000235:genetics / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007109:Immunity / Q000235:genetics; D007136:Immunoglobulins / Q000097:blood / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000097:blood / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018167:Receptors, Calcitriol / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
D000939:Epitopes; D007136:Immunoglobulins; D018167:Receptors, Calcitriol; D007371:Interferon-gamma; D002117:Calcitriol