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...
Autores principales: | , , , , , , |
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Formato: | Articulo |
Lenguaje: | Inglés |
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2015
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Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/86903 |
Aporte de: |
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I19-R120-10915-86903 |
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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 |
work_keys_str_mv |
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bdutipo_str |
Repositorios |
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