Polymeric immunoglobulin receptor-mediated invasion of Streptococcus pneumoniae into host cells requires a coordinate signaling of SRC family of protein-tyrosine kinases, ERK, and c-Jun N-terminal kinase

Vaibhav Agarwal; Tauseef M Asmat; Nina I Dierdorf; Christof R Hauck; Sven Hammerschmidt

doi:10.1074/jbc.M110.172999

Polymeric immunoglobulin receptor-mediated invasion of Streptococcus pneumoniae into host cells requires a coordinate signaling of SRC family of protein-tyrosine kinases, ERK, and c-Jun N-terminal kinase

J Biol Chem. 2010 Nov 12;285(46):35615-23. doi: 10.1074/jbc.M110.172999. Epub 2010 Sep 9.

Authors

Vaibhav Agarwal¹, Tauseef M Asmat, Nina I Dierdorf, Christof R Hauck, Sven Hammerschmidt

Affiliation

¹ Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt Universität Greifswald, Friedrich-Ludwig-Jahn-Strasse 15a, D-17487 Greifswald.

Abstract

Streptococcus pneumoniae are commensals of the human nasopharynx with the capacity to invade mucosal respiratory cells. PspC, a pneumococcal surface protein, interacts with the human polymeric immunoglobulin receptor (pIgR) to promote bacterial adherence to and invasion into epithelial cells. Internalization of pneumococci requires the coordinated action of actin cytoskeleton rearrangements and the retrograde machinery of pIgR. Here, we demonstrate the involvement of Src protein-tyrosine kinases (PTKs), focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) but not p38 mitogen-activated protein kinases (MAPK) in pneumococcal invasion via pIgR. Pharmacological inhibitors of PTKs and MAPKs and genetic interference with Src PTK and FAK functions caused a significant reduction of pIgR-mediated pneumococcal invasion but did not influence bacterial adhesion to host cells. Furthermore, pneumococcal ingestion by host cells induces activation of ERK1/2 and JNK. In agreement with activated JNK, its target molecule and DNA-binding protein c-Jun was phosphorylated. We also show that functionally active Src PTK is essential for activation of ERK1/2 upon pneumococcal infections. In conclusion, these data illustrate the importance of a coordinated signaling between Src PTKs, ERK1/2, and JNK during PspC-pIgR-mediated uptake of pneumococci by host epithelial cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bacterial Adhesion / physiology
Bacterial Proteins / metabolism
Blotting, Western
Cell Line
Cell Line, Tumor
Enzyme Activation
Epithelial Cells / metabolism
Epithelial Cells / microbiology
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
Extracellular Signal-Regulated MAP Kinases / metabolism*
Flavonoids / pharmacology
Focal Adhesion Protein-Tyrosine Kinases / genetics
Focal Adhesion Protein-Tyrosine Kinases / metabolism
Genistein / pharmacology
Host-Pathogen Interactions
Humans
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
JNK Mitogen-Activated Protein Kinases / metabolism*
Microscopy, Confocal
Phosphorylation / drug effects
Protein Kinase Inhibitors / pharmacology
RNA Interference
Receptors, Polymeric Immunoglobulin / genetics
Receptors, Polymeric Immunoglobulin / metabolism*
Signal Transduction / physiology*
Streptococcus pneumoniae / metabolism*
Streptococcus pneumoniae / physiology
Transfection
src-Family Kinases / antagonists & inhibitors
src-Family Kinases / genetics
src-Family Kinases / metabolism*

Substances

Bacterial Proteins
Flavonoids
Protein Kinase Inhibitors
Receptors, Polymeric Immunoglobulin
SpsA protein, Streptococcus pneumoniae
Genistein
Focal Adhesion Protein-Tyrosine Kinases
src-Family Kinases
Extracellular Signal-Regulated MAP Kinases
JNK Mitogen-Activated Protein Kinases
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one