Increased translocation of Escherichia coli and development of arthritis in vitamin A-deficient rats.
We studied the immune response and the colonization pattern in vitamin A-deficient rats that were colonized with the Escherichia coli O6 K13 pOmp 21 strain, which is genetically manipulated to produce ovalbumin and to be resistant to ampicillin. In the vitamin A-deficient rats, the number of bacteria per gram of feces was about five times higher than in the paired fed control rats 4 weeks after colonization. In the control rats, the colon and the lower part of the ileum were colonized, while in the vitamin A-deficient rats all parts of the small intestine, as well as the colon, were heavily inhabited by bacteria. Furthermore, in 75% of the vitamin A-deficient rats, the E. coli bacteria were found in the mesenteric lymph nodes, and in 50% of the rats E. coli were found in the kidneys. These animals also developed severe arthritis. The levels of serum immunoglobulin G (IgG), IgM, IgE, and biliary IgA antibodies against the bacterial antigens were significantly higher in the vitamin A-deficient rats than in the control rats. The number of IgA-producing cells in the lamina propria of the small intestine was significantly lower in the vitamin A-deficient rats than in the control rats; however, there was an increase in the number of CD8+ cells and transforming growth factor beta-producing cells in the lamina propria of the vitamin A-deficient rats. Disturbances in T-cell function were demonstrated, since spleen cells from the vitamin A-deficient rats produced more gamma interferon and interleukin-2 in vitro than control spleen cells. In summary, vitamin A deficiency led to a decrease in the ability to control the localization of intestinal bacteria and an increase in translocation, which was followed by development of arthritis regardless of substantial levels of antibacterial antibodies. The bacterial invasion made the animals hyperresponsive to the bacterial antigens, despite the fact that vitamin A deficiency is normally associated with suppressed antibody production, as previously shown by us and others.
Wiedermann
U
U
Department of Clinical Immunology, University of Göteborg, Sweden.
Hanson
L A
LA
Bremell
T
T
Kahu
H
H
Dahlgren
U I
UI
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001168:Arthritis / Q000209:etiology*; D001646:Bile / Q000276:immunology; D001835:Body Weight; D004927:Escherichia coli Infections / Q000276:immunology*; D007070:Immunoglobulin A / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014802:Vitamin A Deficiency / Q000276:immunology / Q000382:microbiology*
D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D007376:Interleukin-2; D007371:Interferon-gamma