cyclic-gmp and Tuberculosis

Pellicles, a type of biofilm, have gathered a renewed interest in the field of tuberculosis as a structure that mimics some characteristics occurring during M. tuberculosis infection, such as antibiotic recalcitrance and chronicity of infection, and as a source of antigens for humoral response in infected guinea pigs. In other bacteria, it has been well documented that the second messenger c-di-GMP modulates the transition from planktonic cells to biofilm formation. In this work, we used the live vaccine Mycobacterium bovis BCG to determine whether deletion of genes involved in c-di-GMP metabolism would affect interaction with macrophages, capacity to induce immune response in a murine cell line and mice, and how the protein profile was modified when grown as surface pellicles. We found that deletion of the BCG1419c (Delta c-di-GMP phosphodiesterase, ΔPDE) gene, or deletion of the BCG1416c (Delta c-di-GMP diguanylate cyclase, ΔDGC) gene, altered production of TNF-α, IL-6, and IL-1β, in murine macrophages, and resulted in attenuation in intra-macrophage replication. Moreover, in addition to the improved immunogenicity of the BCGΔBCG1419c mutant already reported, deletion of the BCG1416c gene leads to increased T CD4

Topics: Animals; BCG Vaccine; Cyclic GMP; Cytokines; Gene Order; Genetic Vectors; Immunity; Lung; Lymphocyte Activation; Macrophages; Mice; Mycobacterium tuberculosis; T-Lymphocyte Subsets; Tuberculosis; Vaccination; Virulence

Topics: Animals; Cyclic AMP; Cyclic GMP; Guinea Pigs; T-Lymphocytes; Tuberculosis

Topics: Adjuvants, Immunologic; Animals; Cyclic AMP; Cyclic GMP; Guinea Pigs; In Vitro Techniques; Levamisole; Lymphocyte Activation; T-Lymphocytes; Tuberculosis