Abstract
We have investigated the consequences of vitamin A deficiency in a rat model of T-cell-dependent and superantigen-mediated Staphylococcus aureus arthritis. After intravenous inoculation of enterotoxin A-producing staphylococci, the vitamin-A-deficient rats showed a decreased weight gain compared with the paired fed controls despite equal food consumption. The control rats developed arthritis in the first few days after bacterial inoculation, with a peak frequency at day 5, and then gradually recovered; however, the frequency of arthritis 18 days after bacterial inoculation was 86% among the vitamin A-deficient rats and 44% among the control rats. During this period, 3 of 10 deficient rats and 1 of 10 control rats died. Further in vitro analysis revealed that T-cell responses to S. aureus were significantly higher in the vitamin A-deficient rats than in the control animals. In contrast, B-cell reactivity, measured as immunoglobulin levels, autoantibody levels, and specific antibacterial antibody levels in serum, did not differ between the groups. Interestingly, the innate host defense mechanisms against S. aureus were also profoundly affected by vitamin A deficiency. Thus, despite a larger number of circulating phagocytic cells in the vitamin-A-deficient group, the capacity to phagocytize and exert intracellular killing of S. aureus was significantly decreased in comparison with the control rats. Furthermore, serum from the vitamin A-deficient rats inoculated with Staphylococcus aureus displayed decreased complement lysis activity. Our results suggest that the increased susceptibility to S. aureus infection observed in the vitamin-A-deficient rats is due to a concerted action of antigen-specific T-cell hyperactivity, impaired function of the phagocytes, and decreased complement activity.
Full Text
The Full Text of this article is available as a PDF (233.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aarden L. A., De Groot E. R., Schaap O. L., Lansdorp P. M. Production of hybridoma growth factor by human monocytes. Eur J Immunol. 1987 Oct;17(10):1411–1416. doi: 10.1002/eji.1830171004. [DOI] [PubMed] [Google Scholar]
- Abdelnour A., Bremell T., Holmdahl R., Tarkowski A. Clonal expansion of T lymphocytes causes arthritis and mortality in mice infected with toxic shock syndrome toxin-1-producing staphylococci. Eur J Immunol. 1994 May;24(5):1161–1166. doi: 10.1002/eji.1830240523. [DOI] [PubMed] [Google Scholar]
- Abdelnour A., Bremell T., Holmdahl R., Tarkowski A. Role of T lymphocytes in experimental Staphylococcus aureus arthritis. Scand J Immunol. 1994 Apr;39(4):403–408. doi: 10.1111/j.1365-3083.1994.tb03392.x. [DOI] [PubMed] [Google Scholar]
- Arthur P., Kirkwood B., Ross D., Morris S., Gyapong J., Tomkins A., Addy H. Impact of vitamin A supplementation on childhood morbidity in northern Ghana. Lancet. 1992 Feb 8;339(8789):361–362. doi: 10.1016/0140-6736(92)91677-z. [DOI] [PubMed] [Google Scholar]
- Bellinati-Pires R., Carneiro-Sampaio M. M., Colletto G. M. Functional evaluation of human neutrophils. Is the bactericidal activity correlated with nitroblue tetrazolium reduction? J Investig Allergol Clin Immunol. 1992 May-Jun;2(3):146–153. [PubMed] [Google Scholar]
- Bremell T., Holmdahl R., Tarkowski A. Protective role of sialophorin (CD43)-expressing cells in experimental Staphylococcus aureus infection. Infect Immun. 1994 Oct;62(10):4637–4640. doi: 10.1128/iai.62.10.4637-4640.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bremell T., Lange S., Holmdahl R., Rydén C., Hansson G. K., Tarkowski A. Immunopathological features of rat Staphylococcus aureus arthritis. Infect Immun. 1994 Jun;62(6):2334–2344. doi: 10.1128/iai.62.6.2334-2344.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carman J. A., Hayes C. E. Abnormal regulation of IFN-gamma secretion in vitamin A deficiency. J Immunol. 1991 Aug 15;147(4):1247–1252. [PubMed] [Google Scholar]
- Catignani G. L., Bieri J. G. Simultaneous determination of retinol and alpha-tocopherol in serum or plasma by liquid chromatography. Clin Chem. 1983 Apr;29(4):708–712. [PubMed] [Google Scholar]
- Dahlgren U., Ahlstedt S., Andersson T., Hedman L., Hanson L. A. IgA antibodies in rat bile are not solely derived from thoracic duct lymph. Scand J Immunol. 1983 Jun;17(6):569–574. doi: 10.1111/j.1365-3083.1983.tb00825.x. [DOI] [PubMed] [Google Scholar]
- Davis C. Y., Sell J. L. Immunoglobulin concentrations in serum and tissues of vitamin A-deficient broiler chicks after Newcastle disease virus vaccination. Poult Sci. 1989 Jan;68(1):136–144. doi: 10.3382/ps.0680136. [DOI] [PubMed] [Google Scholar]
- Elwing H., Nygren H. Diffusion in gel-enzyme linked immunosorbent assay (DIG-ELISA): a simple method for quantitation of class-specific antibodies. J Immunol Methods. 1979;31(1-2):101–107. doi: 10.1016/0022-1759(79)90290-4. [DOI] [PubMed] [Google Scholar]
- Friedman A., Sklan D. Antigen-specific immune response impairment in the chick as influenced by dietary vitamin A. J Nutr. 1989 May;119(5):790–795. doi: 10.1093/jn/119.5.790. [DOI] [PubMed] [Google Scholar]
- Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
- Goldenberg D. L., Chisholm P. L., Rice P. A. Experimental models of bacterial arthritis: a microbiologic and histopathologic characterization of the arthritis after the intraarticular injections of Neisseria gonorrhoeae, Staphylococcus aureus, group A streptococci, and Escherichia coli. J Rheumatol. 1983 Feb;10(1):5–11. [PubMed] [Google Scholar]
- Goldenberg D. L., Reed J. I. Bacterial arthritis. N Engl J Med. 1985 Mar 21;312(12):764–771. doi: 10.1056/NEJM198503213121206. [DOI] [PubMed] [Google Scholar]
- Helle M., Boeije L., Aarden L. A. Functional discrimination between interleukin 6 and interleukin 1. Eur J Immunol. 1988 Oct;18(10):1535–1540. doi: 10.1002/eji.1830181010. [DOI] [PubMed] [Google Scholar]
- Lissner C. R., Swanson R. N., O'Brien A. D. Genetic control of the innate resistance of mice to Salmonella typhimurium: expression of the Ity gene in peritoneal and splenic macrophages isolated in vitro. J Immunol. 1983 Dec;131(6):3006–3013. [PubMed] [Google Scholar]
- Madjid B., Sirisinha S., Lamb A. J. The effect of vitamin A and protein deficiency on complement levels in rats. Proc Soc Exp Biol Med. 1978 May;158(1):92–95. doi: 10.3181/00379727-158-40147. [DOI] [PubMed] [Google Scholar]
- Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
- Mikhail I. S., Alarcón G. S. Nongonococcal bacterial arthritis. Rheum Dis Clin North Am. 1993 May;19(2):311–331. [PubMed] [Google Scholar]
- Nauss K. M., Mark D. A., Suskind R. M. The effect of vitamin A deficiency on the in vitro cellular immune response of rats. J Nutr. 1979 Oct;109(10):1815–1823. doi: 10.1093/jn/109.10.1815. [DOI] [PubMed] [Google Scholar]
- Ongsakul M., Sirisinha S., Lamb A. J. Impaired blood clearance of bacteria and phagocytic activity in vitamin A-deficient rats. Proc Soc Exp Biol Med. 1985 Feb;178(2):204–208. doi: 10.3181/00379727-178-41999. [DOI] [PubMed] [Google Scholar]
- Pasatiempo A. M., Kinoshita M., Taylor C. E., Ross A. C. Antibody production in vitamin A-depleted rats is impaired after immunization with bacterial polysaccharide or protein antigens. FASEB J. 1990 May;4(8):2518–2527. doi: 10.1096/fasebj.4.8.2110538. [DOI] [PubMed] [Google Scholar]
- Rahmathullah L., Underwood B. A., Thulasiraj R. D., Milton R. C. Diarrhea, respiratory infections, and growth are not affected by a weekly low-dose vitamin A supplement: a masked, controlled field trial in children in southern India. Am J Clin Nutr. 1991 Sep;54(3):568–577. doi: 10.1093/ajcn/54.3.568. [DOI] [PubMed] [Google Scholar]
- Sijtsma S. R., Rombout J. H., Dohmen M. J., West C. E., van der Zijpp A. J. Effect of vitamin A deficiency on the activity of macrophages in Newcastle disease virus-infected chickens. Vet Immunol Immunopathol. 1991 Mar;28(1):17–27. doi: 10.1016/0165-2427(91)90039-f. [DOI] [PubMed] [Google Scholar]
- Sijtsma S. R., Rombout J. H., Kiepurski A., West C. E., van der Zijpp A. J. Changes in lymphoid organs and blood lymphocytes induced by vitamin A deficiency and Newcastle disease virus infection in chickens. Dev Comp Immunol. 1991 Fall;15(4):349–356. doi: 10.1016/0145-305x(91)90027-v. [DOI] [PubMed] [Google Scholar]
- Sommer A., Tarwotjo I., Djunaedi E., West K. P., Jr, Loeden A. A., Tilden R., Mele L. Impact of vitamin A supplementation on childhood mortality. A randomised controlled community trial. Lancet. 1986 May 24;1(8491):1169–1173. doi: 10.1016/s0140-6736(86)91157-8. [DOI] [PubMed] [Google Scholar]
- Tarkowski A., Czerkinsky C., Nilsson L. A. Detection of IgG rheumatoid factor secreting cells in autoimmune MRL/1 mice: a kinetic study. Clin Exp Immunol. 1984 Oct;58(1):7–12. [PMC free article] [PubMed] [Google Scholar]
- West K. P., Jr, Howard G. R., Sommer A. Vitamin A and infection: public health implications. Annu Rev Nutr. 1989;9:63–86. doi: 10.1146/annurev.nu.09.070189.000431. [DOI] [PubMed] [Google Scholar]
- Wiedermann U., Hanson L. A., Bremell T., Kahu H., Dahlgren U. I. Increased translocation of Escherichia coli and development of arthritis in vitamin A-deficient rats. Infect Immun. 1995 Aug;63(8):3062–3068. doi: 10.1128/iai.63.8.3062-3068.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wiedermann U., Hanson L. A., Holmgren J., Kahu H., Dahlgren U. I. Impaired mucosal antibody response to cholera toxin in vitamin A-deficient rats immunized with oral cholera vaccine. Infect Immun. 1993 Sep;61(9):3952–3957. doi: 10.1128/iai.61.9.3952-3957.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wiedermann U., Hanson L. A., Kahu H., Dahlgren U. I. Aberrant T-cell function in vitro and impaired T-cell dependent antibody response in vivo in vitamin A-deficient rats. Immunology. 1993 Dec;80(4):581–586. [PMC free article] [PubMed] [Google Scholar]
- Zhao Y. X., Abdelnour A., Holmdahl R., Tarkowski A. Mice with the xid B cell defect are less susceptible to developing Staphylococcus aureus-induced arthritis. J Immunol. 1995 Aug 15;155(4):2067–2076. [PubMed] [Google Scholar]