IDEHU   05542
INSTITUTO DE ESTUDIOS DE LA INMUNIDAD HUMORAL PROF. RICARDO A. MARGNI
Unidad Ejecutora - UE
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, MS; FERNANDEZ, AG; FOSSATI, CA; BALDI, PC
Lugar:
Los Cocos, Córdoba
Reunión:
Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología; 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.