CONICET | Buscador de Institutos y Recursos Humanos

AbstractBoth CCL20 and human β-defensin 2 (hBD2) interact with the same membrane receptor anddisplay chemotactic and antimicrobial activities. They are produced by airway epithelia inresponse to infectious agents and proinflammatory cytokines. Whereas Brucella spp. caninfect humans through inhalation, their ability to induce CCL20 and hBD2 in lung cells isunknown. Here we show that B. abortus induces CCL20 expression in human alveolar(A549) or bronchial (Calu-6) epithelial cell lines, primary alveolar epithelial cells, primaryhuman monocytes, monocyte-derived macrophages and the monocytic cell line THP-1.CCL20 expression was mainly mediated by JNK1/2 and NF-kB in both Calu-6 and THP-1cells. CCL20 secretion was markedly induced in A549, Calu-6 and THP-1 cells by heat-killedB. abortus or a model Brucella lipoprotein (L-Omp19) but not by the B. abortus lipopolysaccharide(LPS). Accordingly, CCL20 production by B. abortus-infected cells was stronglyTLR2-dependent. Whereas hBD2 expression was not induced by B. abortus infection, it wassignificantly induced in A549 cells by conditioned media from B. abortus-infected THP-1monocytes (CMB). A similar inducing effect was observed on CCL20 secretion. Experimentsusing blocking agents revealed that IL-1β, but not TNF-α, was involved in the induction ofhBD2 and CCL20 secretion by CMB. In the in vitro antimicrobial assay, the lethal dose (LD)50 of CCL20 for B. abortus (>50 μg/ml) was markedly higher than that against E. coli (1.5 μg/ml) or a B. abortus mutant lacking the O polysaccharide in its LPS (8.7 ug/ml). hBD2 did notkill any of the B. abortus strains at the tested concentrations. These results show that humanlung epithelial cells secrete CCL20 and hBD2 in response to B. abortus and/or to cytokinesproduced by infected monocytes. Whereas these molecules do not seem to exert antimicrobialactivity against this pathogen, they could recruit immune cells to the infection site.PLOS