Low calcium diet and 1,25-dihydroxyvitamin D-3 infusion modulate immune responses during Mycobacterium paratuberculosis infection in beige mice

A 12-month study was conducted to evaluate the effects of feeding a low calcium (Ca) diet or 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) infusion on the persistence of Mycobacterium paratuberculosis infection using a mouse model, Male beige mice 6-8 weeks of age were assigned to one of the following treatments: (1) non-infected, (2) infected, (3) non-infected/1,25(OH)(2)D-3, (4) infected/1,25(OH)(2)D-3, and (5) infected/low Ca (0.15%) diet, Infected mice were inoculated intravenously with live M. paratuberculosis. At 1, 6 and 12 months postinfection, mice in Treatments 3 and 4 were implanted subcutaneously with mini-osmotic pumps to deliver 1,25(OH)(2)D-3. Infusion with 1,25(OH)(2)D-3 exacerbated M. paratuberculosis infection in most tissues at all time points, Mice infused with 1,25(OH)(2)D-3 had higher bacterial counts in spleen, liver, and ileum compared with control infected mice after 1 month of infection. In contrast, feeding a low Ca diet reduced the number of viable organisms cultured from the liver and ileum of infected mice, Plasma Ca and 1,25(OH)(2)D-3 were increased in mice infused with 1,25(OH)(2)D-3 at all time points but values for low Ca mice were not different than for non-infused mice. Splenocyte production of TNF, IL-1 and IL-6 was higher for mice fed the low Ca diet compared with control infected mice after 1 month of infection, Inducible IL-6 activity remained higher for this treatment at 6 months postinfection. These results suggest that feeding a low Ca diet to mice chronically infected with M. paratuberculosis appears to enhance their ability to clear the infection in a manner distinct from any effect of 1,25(OH)(2)D-3.