E-044. The Role of 1, 25(OH)2 D3 in the Pathogenesis of and Immunity against Chlamydia

Q. He1,2, M. Thierry-Palmer1, K. Joseph2, F. Eko1, D. Lyn1, G. Ananaba1, C. Black2, J. Igietseme1,2;
1Morehouse Sch. of Med., Atlanta, GA, 2CDC, Atlanta, GA.

Genital chlamydial infection is the most common bacterial STD in several industrialized nations. The columnar epithelial cell is the target of infection in the reproductive tract. Dendritic cells (DCs) and Th1 immune response are required for induction of protective immunity. A better understanding of the factors that influence chlamydial infectivity of epithelial cells and the factors that affect the ability of DCs to induce immune response will be important for unraveling chlamydial pathogenesis and protective immunity. 1, 25 Dihydroxyvitamin D3 (1, 25-(OH) 2 D3), the physiologically active form of vitamin D3, possesses strong immunomodulating properties. The nuclear vitamin D receptor (VDR), which mediated the biological effects of 1, 25-(OH)2 D3, has been discovered in various immune cell lines, including T and B cell and dendritic cells. These discoveries provide a link between vitamin D deficiency and the occurrence of respiratory infections, diarrheal disease, and tuberculosis. It is uncertain, however, whether the vitamin D hormone is associated with health and immunological outcomes related to Chlamydia infection. We investigated the hypothesis that 1, 25-(OH)2 D3 influences chlamydial colonization and replication in epithelial cells and also regulates DC function leading to the development of immunity against Chlamydia. Hela cells were treated with different doses of 1, 25-(OH)2 D3 (10-7, 2X10-7, 10-8 and 10-9 M) and infected with Chlamydia. Infectivity titers were 25 and 30 times higher in non-treated cells than in1, 25-(OH)2 D3 treated (10-8 and 10-9 M ) Hela cells respectively (56 x 109 ± 2.9 x 106 IFU/ml versus 2.2 x 109 ± 0.7 x 109 IFU/ml and 1.8 x 109 ± 0.7 x 109 IFU/ml). To investigate the effect of 1, 25-(OH)2 D3 on chlamydial antigen handling by DC, we analyzed the time course of chlamydial up-take (using confocal microscopy) by treated or non-treated DCs with 1, 25-(OH)2 D3. Chlamydia internalized into the 1, 25-(OH)2 D3-treated DC, whereas internalization into non-treated DC was barely detectable The results would suggest that Vit D treatment may limit chlamydial replication in epithelial cells although it may enhance DC uptake and immune response against Chlamydia.

232/E. Innate Immunity in Host Defense

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