Publication:
Klebsiella pneumoniae outer membrane protein A is required to prevent the activation of airway epithelial cells

Date

2011

Authors

March, Catalina
Moranta, David
Regueiro, Verónica
Llobet, Enrique
Tomás, Anna
Garmendia García, Juncal
Bengoechea Alonso, José Antonio

Director

Publisher

American Society for Biochemistry and Molecular Biology
Acceso abierto / Sarbide irekia
Artículo / Artikulua
Versión publicada / Argitaratu den bertsioa

Project identifier

Abstract

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.

Description

Keywords

Klebsiella pneumoniae, Host inflammatory response, Airway cell responses

Department

IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua

Faculty/School

Degree

Doctorate program

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© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

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