CCL20 and Beta-defensin 2 Production by Human Lung Epithelial Cells and Macrophages in Response to Brucella abortus Infection

HIELPOS S; FERRERO MC,; FERNANDEZ AG; BONETTO JOSEFINA; GIAMBARTOLOMEI GH; FOSSATI, CA; BALDI PC

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2015 vol. 10 p. 1 - 23

1932-6203

CCL20 andBeta-defensin 2 Production by Human Lung Epithelial Cells and Macrophages inResponse to Brucella abortusInfection Both CCL20 and human β-defensin 2 (hBD2) interact withthe same membrane receptor anddisplay chemotactic and antimicrobial activities. Theyare produced by airway epithelia inresponse to infectious agents and proinflammatorycytokines. Whereas Brucella spp. caninfect humans through inhalation, their ability toinduce CCL20 and hBD2 in lung cells isunknown. Here we show that B. abortus induces CCL20expression in human alveolar(A549) or bronchial (Calu-6) epithelial cell lines,primary alveolar epithelial cells, primaryhuman monocytes, monocyte-derived macrophages and themonocytic cell line THP-1.CCL20 expression was mainly mediated by JNK1/2 andNF-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 notinduced by B. abortus infection, it wassignificantly induced in A549 cells by conditionedmedia from B. abortus-infected THP-1monocytes (CMB). A similar inducing effect wasobserved on CCL20 secretion. Experimentsusing blocking agents revealed that IL-1β, but notTNF-α, was involved in the induction ofhBD2 and CCL20 secretion by CMB. In the in vitroantimicrobial assay, the lethal dose (LD)50 of CCL20 for B. abortus (>50 μg/ml) was markedlyhigher than that against E. coli (1.5 μg/ml) or a B. abortus mutant lacking the Opolysaccharide in its LPS (8.7 ug/ml). hBD2 did notkill any of the B. abortus strains at the testedconcentrations. These results show that humanlung epithelial cells secrete CCL20 and hBD2 inresponse to B. abortus and/or to cytokinesproduced by infected monocytes. Whereas thesemolecules do not seem to exert antimicrobialactivity against this pathogen, they could recruit immune cells to theinfection site.