In spite of advances in immunology on mycobacterial
infection, there are few studies on the role of anti-microbial
peptides in
tuberculosis. The
cathelin-related anti-microbial
peptide (
CRAMP) is the only
cathelicidin isolated from mice. In this work we investigated the cellular sources and the production kinetics of this molecule during experimental
tuberculosis, using two well-characterized models of latent or
chronic infection and progressive disease. The lung of non-infected control mice expressed
CRAMP at very low levels. In both models of experimental
tuberculosis the main cells immunolabelled for
CRAMP were bronchial epithelial cells, macrophages and pneumocytes types II and I. After intratracheal
infection with a high bacilli dose (H37Rv strain) in Balb/c mice to produce progressive disease, a high
CRAMP gene expression was induced showing three peaks: very early after 1 day of
infection, at day 21 when the peak of protective immunity in this model is raised, and at day 28 when the progressive phase starts and the immunoelectronmicroscopy study showed intense immunolabelling in the cell wall and cytoplasm of intracellular bacilli, as well as in cytoplasmic vacuoles. Interestingly, at day 60 post-
infection, when advanced progressive disease is well established, characterized by high bacillary loads and extensive tissue damage,
CRAMP gene expression decreased but strong
CRAMP immunostaining was detected in vacuolated macrophages filled with bacilli. Thus,
cathelicidin is highly produced during experimental
pulmonary tuberculosis from diverse cellular sources and could have significant participation in its pathogenesis.