SummaryCCL20 is a chemokine that attracts immature dendritic cells. We show that monocytes, cells characteristic of the innate immune response, infected with Mycobacterium tuberculosis express the CCL20 gene at a much higher level than the same cells infected with non-tuberculous mycobacteria. Interferon (IFN)-g, a fundamental cytokine in the immune response to tuberculosis, strongly inhibits both the transcription and the translation of CCL20. We have also confirmed that dendritic cells are a suitable host for mycobacteria proliferation, although CCL20 does not seem to influence their intracellular multiplication rate. The chemokine, however, down-regulates the characteristic production of reactive oxygen species (ROS) induced by M. tuberculosis in monocytes, which may affect the activity of the cells. Apoptosis mediated by the mycobacteria, possibly ROS-dependent, was also inhibited by CCL20.

Non-pathogenic mycobacteria, like Mycobacterium gordonae, are rarely associated to disease. The analysis of the mechanisms which are successful against them in the human host may provide useful information to understand why they fail against the pathogenic M. tuberculosis. We have developed an infection model in human phagocytes to test their ability to kill two strains of M. gordonae , HL184Gand an attenuated variety, HL184Gat. As controls we included a strain of M. tuberculosis (HL186T) and another of L. pneumophila (ATCC13151). We observed that human phagocytes lack the intrinsic ability to eliminate either M. gordonae or M. tuberculosis, but they kill the attenuated strain. We could observe a relationship between pathogenicity and the pattern of cytokine production. Thus, both the pathogenic M. tuberculosis and L. pneumophila, but not the nonpathogenic M. gordonae, induced the production of significantly different levels of IL-1β, IL-6 and TNF-α in monocytes and IL-8 in neutrophils. Although both monocytes and neutrophils killed HL184Gat, but not HL184G, the patterns of cytokine production induced by either strain were identical. Addition of INF-γ and/or TNF-α did not improve the antimycobacterial activity of phagocytes.

Two of the better characterized antimicrobial mechanisms displayed by human neutrophils are the reactive oxygen species (ROS) production and the induction of apoptosis. Their importance in mycobacterial infections is, however, controversial and we aimed to analyze them simultaneously in neutrophils infected with either M.tuberculosis or the non-pathogenic M. gordonae. Neither species is eliminated by neutrophils but the pattern exhibited for both activities is completely different. M. tuberculosis induces ROS production and apoptosis but M. gordonae does not.Additional evidence was provided by an attenuated strain of M. gordonae that, although it has become susceptible to the antimicrobial activity of neutrophils, it still does not promote ROS production or apoptosis. Therefore no relationship could be established between any of these activities and the ability of neutrophils to kill mycobacteria. We have also observed that neutrophil concentration, a variable that is important in the antimicrobial activity against other pathogens, has no influence in the mycobacterial intracellular growth.