Klebsiella pneumoniae outer membrane protein A is required to prevent the activation of airway epithelial cells
Fecha
2011Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión publicada / Argitaratu den bertsioa
Impacto
|
10.1074/jbc.m110.181008
Resumen
Outer membrane protein A (OmpA) is a class of proteins
highly conserved among the Enterobacteriaceae family and
throughout evolution. Klebsiella pneumoniae is a capsulated
Gram-negative pathogen. It is an important cause of community-
acquired and nosocomial pneumonia. Evidence indicates
that K. pneumoniae infections are characterized by a lack of an
early inflammatory response. Data from our lab ...
[++]
Outer membrane protein A (OmpA) is a class of proteins
highly conserved among the Enterobacteriaceae family and
throughout evolution. Klebsiella pneumoniae is a capsulated
Gram-negative pathogen. It is an important cause of community-
acquired and nosocomial pneumonia. Evidence indicates
that K. pneumoniae infections are characterized by a lack of an
early inflammatory response. Data from our laboratory indicate
that K. pneumoniae CPS helps to suppress the host inflammatory
response. However, it is unknown whether K. pneumoniae
employs additional factors to modulate host inflammatory
responses. Here, we report that K. pneumoniaeOmpAis important
for immune evasion in vitro and in vivo. Infection of A549
and normal human bronchial cells with 52OmpA2, an ompA
mutant, increased the levels of IL-8. 52145- ΔwcaK2ompA,
which does not express CPS and ompA, induced the highest levels
of IL-8. Both mutants could be complemented. In vivo,
52OmpA2 induced higher levels of tnfα, kc, and il6 than the wild
type. ompA mutants activated NF- κB, and the phosphorylation
of p38, p44/42, and JNK MAPKs and IL-8 induction was via
NF-κB-dependent and p38- and p44/42-dependent pathways.
52OmpA2 engaged TLR2 and -4 to activate NF-κB, whereas
52145- ΔwcaK2ompA activated not only TLR2 and TLR4 but
also NOD1. Finally, we demonstrate that the ompA mutant is
attenuated in the pneumonia mouse model. The results of this
study indicate that K. pneumoniae OmpA contributes to attenuate
airway cell responses. This may facilitate pathogen survival
in the hostile environment of the lung. [--]
Materias
Klebsiella pneumoniae,
Host inflammatory response,
Airway cell responses
Editor
American Society for Biochemistry and Molecular Biology
Publicado en
Journal of Biological Chemistry, vol. 286, no. 12, pp. 9956–9967, March 25, 2011
Departamento
Universidad Pública de Navarra/Nafarroako Unibertsitate Publikoa. IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
Versión del editor
Entidades Financiadoras
This work was supported by Fondo de Investigación Sanitaria Grant PI06/1629, ERA-NET Pathogenomics Grants GEN2006-27776-C2–2-E/PAT and SAF2008-04353-E, and Biomedicine Program Grant SAF2009-07885 from the Ministerio de Ciencia e Innovación (to J. A. B.).