INVESTIGADORES
FOSSATI Carlos Alberto
congresos y reuniones científicas
Título:
CCL20 IS SECRETED BY LUNG EPITHELIAL CELLS IN RESPONSE TO BRUCELLA ABORTUS INFECTION AND HAS ANTIMICROBIAL ACTIVITY AGAINST THIS PATHOGEN
Autor/es:
FERRERO MC,; HIELPOS S; FERNANDEZ AG; FOSSATI CA; BALDI PC,
Lugar:
Los Cocos, Córdoba
Reunión:
Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología. Los Cocos, Córdoba; 2013
Institución organizadora:
Sociedad Argentina de Inmunología
Resumen:
Although Brucella frequently infects humans through inhalation,
its interaction with pulmonary cells has been overlooked. CCL20 is a potent
chemoattractant for immature dendritic cells and T cells. Antimicrobial
activities for CCL20 have been recently reported. We evaluated the
antimicrobial activity of CCL20 against Brucella abortus, and whether
this pathogen induces the secretion of CCL20 in human bronchial (Calu-6) and
alveolar (A549) epithelial cells and macrophages (PMA-treated THP-1 cells).
CCL20 killed B. abortus with a lethal dose (LD50, achieving 50%
reduction of CFU) of 50 ug/ml. Cells were infected for 2 hours at
multiplicities of infection (MOI) of 50 to 500 bacteria/cell (epithelial cells)
or 10 to 100 bacteria/cell (macrophages). At 24 and 48 h post-infection CCL20
was measured by ELISA in culture supernatants. Infection significantly
increased the production of CCL20 in macrophages and bronchial epithelial cells
in a MOI-dependent manner (p<0.05). Both cell types also secreted CCL20 in
response to heat-killed B. abortus and to PAMPs used for comparison
(flagellin, Pam3Cys and E. coli LPS). In contrast, B. abortus LPS
did not induce CCL20 secretion. Whereas the infection of A549 alveolar cells
induced a slight, non-significant increase of CCL20 (p>0.05), the
stimulation of these cells with conditioned medium from B. abortus-infected
macrophages (CoIM) induced CCL20 secretion in a dose dependent manner
(p<0.05). Neutralization assays with the antagonist of IL-1β receptor (IL-1Ra) showed that IL-1β present in CoIM is mostly responsible for this
induction, whereas an anti-TNFα antibody had no
effect. This study shows that bronchial epithelial cells and macrophages
secrete CCL20 upon infection with B. abortus or stimulation with its
antigens, while alveolar epithelial cells do so after stimulation by factors
secreted by infected macrophages. CCL20
has antimicrobial activity against B. abortus.