Klebsiella pneumoniae capsule polysaccharide impedes the expression of beta-defensins by airway epithelial cells.
Human beta-defensins (hBDs) contribute to the protection of the respiratory tract against pathogens. It is reasonable to postulate that pathogens have developed countermeasures to resist them. Klebsiella pneumoniae capsule polysaccharide (CPS), but not the lipopolysaccharide O antigen, mediated resistance against hBD1 and hBD2. hBD3 was the most potent hBD against Klebsiella. We investigated the possibility that as a strategy for survival in the lung, K. pneumoniae may not activate the expression of hBDs. Infection of A549 and normal human bronchial cells with 52145-Deltawca(K2), a CPS mutant, increased the expression of hBD2 and hBD3. Neither the wild type nor the lipopolysaccharide O antigen mutant increased the expression of hBDs. In vivo, 52145-Deltawca(K2) induced higher levels of mBD4 and mBD14, possible mouse orthologues of hBD2 and hBD3, respectively, than the wild type. 52145-Deltawca(K2)-dependent upregulation of hBD2 occurred via NF-kappaB and mitogen-activated protein kinases (MAPKs) p44/42, Jun N-terminal protein kinase (JNK)-dependent pathways. The increase in hBD3 expression was dependent on the MAPK JNK. 52145-Deltawca(K2) engaged Toll-like receptors 2 and 4 (TLR2 and TLR4) to activate hBD2, whereas hBD3 expression was dependent on NOD1. K. pneumoniae induced the expression of CYLD and MKP-1, which act as negative regulators for 52145-Deltawca(K2)-induced expression of hBDs. Bacterial engagement of pattern recognition receptors induced CYLD and MKP-1, which may initiate the attenuation of proinflammatory pathways. The results of this study indicate that K. pneumoniae CPS not only protects the pathogen from the bactericidal action of defensins but also impedes their expression. These features of K. pneumoniae CPS may facilitate pathogen survival in the hostile environment of the lung.
Moranta
David
D
Program Infection and Immunity, Fundación Caubet- CIMERA Illes Balears, Recinto Hospital Joan March, 07110 Bunyola, Spain.
Regueiro
Verónica
V
March
Catalina
C
Llobet
Enrique
E
Margareto
Javier
J
Larrarte
Eider
E
Larrate
Eider
E
Garmendia
Junkal
J
Bengoechea
José A
JA
D000818:Animals; D016667:Bacterial Capsules / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology*; D005260:Female; D017353:Gene Deletion; D017930:Genes, Reporter; D006801:Humans; D007710:Klebsiella Infections / Q000276:immunology; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D023083:beta-Defensins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
D023083:beta-Defensins; D008156:Luciferases