CCL20 and beta-defensin 2 production by human lung epithelial cells and macrophages in response to <i>Brucella abortus</i> infection

Both CCL20 and human β-defensin 2 (hBD2) interact with the same membrane receptor and display chemotactic and antimicrobial activities. They are produced by airway epithelia in response to infectious agents and proinflammatory cytokines. Whereas <i>Brucella</i> spp. can infect humans thr...

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Autores principales: Hielpos, M. Soledad, Ferrero, Mariana C., Fernández, Andrea G., Bonetto, Josefina, Giambartolomei, Guillermo H., Fossati, Carlos Alberto, Baldi, Pablo C.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2015
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/86903
Aporte de:
id I19-R120-10915-86903
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Ciencias Médicas
Brucella abortus
Infection
spellingShingle Ciencias Exactas
Ciencias Médicas
Brucella abortus
Infection
Hielpos, M. Soledad
Ferrero, Mariana C.
Fernández, Andrea G.
Bonetto, Josefina
Giambartolomei, Guillermo H.
Fossati, Carlos Alberto
Baldi, Pablo C.
CCL20 and beta-defensin 2 production by human lung epithelial cells and macrophages in response to <i>Brucella abortus</i> infection
topic_facet Ciencias Exactas
Ciencias Médicas
Brucella abortus
Infection
description Both CCL20 and human β-defensin 2 (hBD2) interact with the same membrane receptor and display chemotactic and antimicrobial activities. They are produced by airway epithelia in response to infectious agents and proinflammatory cytokines. Whereas <i>Brucella</i> spp. can infect humans through inhalation, their ability to induce CCL20 and hBD2 in lung cells is unknown. Here we show that <i>B. abortus</i> induces CCL20 expression in human alveolar (A549) or bronchial (Calu-6) epithelial cell lines, primary alveolar epithelial cells, primary human 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-1 cells. CCL20 secretion was markedly induced in A549, Calu-6 and THP-1 cells by heat-killed <i>B. abortus</i> or a model <i>Brucella</i> lipoprotein (L-Omp19) but not by the <i>B. abortus</i> lipopolysaccharide (LPS). Accordingly, CCL20 production by <i>B. abortus</i>-infected cells was strongly TLR2-dependent. Whereas hBD2 expression was not induced by <i>B. abortus</i> infection, it was significantly induced in A549 cells by conditioned media from <i>B. abortus</i>-infected THP-1 monocytes (CMB). A similar inducing effect was observed on CCL20 secretion. Experiments using blocking agents revealed that IL-1β, but not TNF-α, was involved in the induction of hBD2 and CCL20 secretion by CMB. In the <i>in vitro</i> antimicrobial assay, the lethal dose (LD) 50 of CCL20 for <i>B. abortus</i> (>50 μg/ml) was markedly higher than that against <i>E. coli</i> (1.5 μg/ml) or a <i>B. abortus</i> mutant lacking the O polysaccharide in its LPS (8.7 ug/ml). hBD2 did not kill any of the <i>B. abortus</i> strains at the tested concentrations. These results show that human lung epithelial cells secrete CCL20 and hBD2 in response to <i>B. abortus</i> and/or to cytokines produced by infected monocytes. Whereas these molecules do not seem to exert antimicrobial activity against this pathogen, they could recruit immune cells to the infection site.
format Articulo
Articulo
author Hielpos, M. Soledad
Ferrero, Mariana C.
Fernández, Andrea G.
Bonetto, Josefina
Giambartolomei, Guillermo H.
Fossati, Carlos Alberto
Baldi, Pablo C.
author_facet Hielpos, M. Soledad
Ferrero, Mariana C.
Fernández, Andrea G.
Bonetto, Josefina
Giambartolomei, Guillermo H.
Fossati, Carlos Alberto
Baldi, Pablo C.
author_sort Hielpos, M. Soledad
title CCL20 and beta-defensin 2 production by human lung epithelial cells and macrophages in response to <i>Brucella abortus</i> infection
title_short CCL20 and beta-defensin 2 production by human lung epithelial cells and macrophages in response to <i>Brucella abortus</i> infection
title_full CCL20 and beta-defensin 2 production by human lung epithelial cells and macrophages in response to <i>Brucella abortus</i> infection
title_fullStr CCL20 and beta-defensin 2 production by human lung epithelial cells and macrophages in response to <i>Brucella abortus</i> infection
title_full_unstemmed CCL20 and beta-defensin 2 production by human lung epithelial cells and macrophages in response to <i>Brucella abortus</i> infection
title_sort ccl20 and beta-defensin 2 production by human lung epithelial cells and macrophages in response to <i>brucella abortus</i> infection
publishDate 2015
url http://sedici.unlp.edu.ar/handle/10915/86903
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