Abstract
The interaction between mycobacteria and epithelium is unexplored, but may determine the outcome of the infection. We have analyzed the role of two G protein-coupled receptors, CXCR1 and CXCR2 that are important regulators of many pulmonary diseases. We found that mycobacteria significantly increased the expression of both CXCR1 and CXCR2 on alveolar epithelial cells and both receptors were found to be important for neutrophil diapedesis across primary endothelial cells towards infected mucosa. Mycobacteria, lipoarabinomannan or 19-kDa glycolipoprotein up-regulated the inhibitory G protein-coupled receptor kinase (GRK)2, while GRK3 was less affected. Mycobacteria-induced GRK2 up-regulation decreased chemokine transcription and secretion thereby affecting the neutrophil recruitment to infected mucosa. These events were completely abolished by blocking these receptors prior to infection as the blocking increased epithelial immune responses. We have identified novel interactions occurring in the initial phase of mycobacterial infections by which mycobacterial manipulate epithelial inflammatory responses.
Copyright © 2012 Elsevier GmbH. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Cell Line
-
Cell Movement / drug effects
-
Chemokines / genetics
-
Chemokines / immunology
-
Coculture Techniques
-
Epithelial Cells / drug effects
-
Epithelial Cells / immunology*
-
Epithelial Cells / microbiology
-
G-Protein-Coupled Receptor Kinase 2 / genetics
-
G-Protein-Coupled Receptor Kinase 2 / immunology*
-
G-Protein-Coupled Receptor Kinase 3 / genetics
-
G-Protein-Coupled Receptor Kinase 3 / immunology
-
Gene Expression Regulation
-
Host-Pathogen Interactions / immunology
-
Human Umbilical Vein Endothelial Cells / immunology
-
Human Umbilical Vein Endothelial Cells / microbiology
-
Humans
-
Lipopolysaccharides / pharmacology
-
Mycobacterium bovis / growth & development
-
Mycobacterium bovis / immunology*
-
Neutrophils / immunology
-
Neutrophils / microbiology
-
Receptors, Interleukin-8A / genetics
-
Receptors, Interleukin-8A / immunology*
-
Receptors, Interleukin-8B / genetics
-
Receptors, Interleukin-8B / immunology*
-
Respiratory Mucosa / drug effects
-
Respiratory Mucosa / immunology*
-
Respiratory Mucosa / microbiology
Substances
-
Chemokines
-
Lipopolysaccharides
-
Receptors, Interleukin-8A
-
Receptors, Interleukin-8B
-
lipoarabinomannan
-
G-Protein-Coupled Receptor Kinase 3
-
GRK2 protein, human
-
GRK3 protein, human
-
G-Protein-Coupled Receptor Kinase 2