Activation of brain endothelium by pneumococcal neuraminidase NanA promotes bacterial internalization

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Activation of brain endothelium by pneumococcal neuraminidase NanA promotes bacterial internalization. / Banerjee, Anirban; Van Sorge, Nina M; Sheen, Tamsin R; Uchiyama, Satoshi; Mitchell, Tim J; Doran, Kelly S.

In: Cellular Microbiology, Vol. 12, No. 11, 11.2010, p. 1576-88.

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Banerjee, Anirban ; Van Sorge, Nina M ; Sheen, Tamsin R ; Uchiyama, Satoshi ; Mitchell, Tim J ; Doran, Kelly S. / Activation of brain endothelium by pneumococcal neuraminidase NanA promotes bacterial internalization. In: Cellular Microbiology. 2010 ; Vol. 12, No. 11. pp. 1576-88.

Bibtex

@article{36cf7f627545419d86b3272645ccb5c7,
title = "Activation of brain endothelium by pneumococcal neuraminidase NanA promotes bacterial internalization",
abstract = "Streptococcus pneumoniae (SPN), the leading cause of meningitis in children and adults worldwide, is associated with an overwhelming host inflammatory response and subsequent brain injury. Here we examine the global response of the blood-brain barrier to SPN infection and the role of neuraminidase A (NanA), an SPN surface anchored protein recently described to promote central nervous system tropism. Microarray analysis of human brain microvascular endothelial cells (hBMEC) during infection with SPN or an isogenic NanA-deficient (ΔnanA) mutant revealed differentially activated genes, including neutrophil chemoattractants IL-8, CXCL-1, CXCL-2. Studies using bacterial mutants, purified recombinant NanA proteins and in vivo neutrophil chemotaxis assays indicated that pneumococcal NanA is necessary and sufficient to activate host chemokine expression and neutrophil recruitment during infection. Chemokine induction was mapped to the NanA N-terminal lectin-binding domain with a limited contribution of the sialidase catalytic activity, and was not dependent on the invasive capability of the organism. Furthermore, pretreatment of hBMEC with recombinant NanA protein significantly increased bacterial invasion, suggesting that NanA-mediated activation of hBMEC is a prerequisite for efficient SPN invasion. These findings were corroborated in an acute murine infection model where we observed less inflammatory infiltrate and decreased chemokine expression following infection with the ΔnanA mutant.",
keywords = "Animals, Blood-Brain Barrier, Brain, Chemokine CCL20, Chemokine CXCL1, Chemokine CXCL2, Chemotaxis, Leukocyte, Endothelial Cells, Endothelium, Vascular, Gene Expression Profiling, Humans, Interleukin-8, Lectins, Meningitis, Pneumococcal, Mice, Mutation, Neuraminidase, Neutrophil Infiltration, Neutrophils, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Signal Transduction, Streptococcus pneumoniae",
author = "Anirban Banerjee and {Van Sorge}, {Nina M} and Sheen, {Tamsin R} and Satoshi Uchiyama and Mitchell, {Tim J} and Doran, {Kelly S}",
note = "{\textcopyright} 2010 Blackwell Publishing Ltd.",
year = "2010",
month = nov,
doi = "10.1111/j.1462-5822.2010.01490.x",
language = "English",
volume = "12",
pages = "1576--88",
journal = "Cellular Microbiology",
issn = "1462-5814",
publisher = "Wiley",
number = "11",

}

RIS

TY - JOUR

T1 - Activation of brain endothelium by pneumococcal neuraminidase NanA promotes bacterial internalization

AU - Banerjee, Anirban

AU - Van Sorge, Nina M

AU - Sheen, Tamsin R

AU - Uchiyama, Satoshi

AU - Mitchell, Tim J

AU - Doran, Kelly S

N1 - © 2010 Blackwell Publishing Ltd.

PY - 2010/11

Y1 - 2010/11

N2 - Streptococcus pneumoniae (SPN), the leading cause of meningitis in children and adults worldwide, is associated with an overwhelming host inflammatory response and subsequent brain injury. Here we examine the global response of the blood-brain barrier to SPN infection and the role of neuraminidase A (NanA), an SPN surface anchored protein recently described to promote central nervous system tropism. Microarray analysis of human brain microvascular endothelial cells (hBMEC) during infection with SPN or an isogenic NanA-deficient (ΔnanA) mutant revealed differentially activated genes, including neutrophil chemoattractants IL-8, CXCL-1, CXCL-2. Studies using bacterial mutants, purified recombinant NanA proteins and in vivo neutrophil chemotaxis assays indicated that pneumococcal NanA is necessary and sufficient to activate host chemokine expression and neutrophil recruitment during infection. Chemokine induction was mapped to the NanA N-terminal lectin-binding domain with a limited contribution of the sialidase catalytic activity, and was not dependent on the invasive capability of the organism. Furthermore, pretreatment of hBMEC with recombinant NanA protein significantly increased bacterial invasion, suggesting that NanA-mediated activation of hBMEC is a prerequisite for efficient SPN invasion. These findings were corroborated in an acute murine infection model where we observed less inflammatory infiltrate and decreased chemokine expression following infection with the ΔnanA mutant.

AB - Streptococcus pneumoniae (SPN), the leading cause of meningitis in children and adults worldwide, is associated with an overwhelming host inflammatory response and subsequent brain injury. Here we examine the global response of the blood-brain barrier to SPN infection and the role of neuraminidase A (NanA), an SPN surface anchored protein recently described to promote central nervous system tropism. Microarray analysis of human brain microvascular endothelial cells (hBMEC) during infection with SPN or an isogenic NanA-deficient (ΔnanA) mutant revealed differentially activated genes, including neutrophil chemoattractants IL-8, CXCL-1, CXCL-2. Studies using bacterial mutants, purified recombinant NanA proteins and in vivo neutrophil chemotaxis assays indicated that pneumococcal NanA is necessary and sufficient to activate host chemokine expression and neutrophil recruitment during infection. Chemokine induction was mapped to the NanA N-terminal lectin-binding domain with a limited contribution of the sialidase catalytic activity, and was not dependent on the invasive capability of the organism. Furthermore, pretreatment of hBMEC with recombinant NanA protein significantly increased bacterial invasion, suggesting that NanA-mediated activation of hBMEC is a prerequisite for efficient SPN invasion. These findings were corroborated in an acute murine infection model where we observed less inflammatory infiltrate and decreased chemokine expression following infection with the ΔnanA mutant.

KW - Animals

KW - Blood-Brain Barrier

KW - Brain

KW - Chemokine CCL20

KW - Chemokine CXCL1

KW - Chemokine CXCL2

KW - Chemotaxis, Leukocyte

KW - Endothelial Cells

KW - Endothelium, Vascular

KW - Gene Expression Profiling

KW - Humans

KW - Interleukin-8

KW - Lectins

KW - Meningitis, Pneumococcal

KW - Mice

KW - Mutation

KW - Neuraminidase

KW - Neutrophil Infiltration

KW - Neutrophils

KW - Oligonucleotide Array Sequence Analysis

KW - Polymerase Chain Reaction

KW - Signal Transduction

KW - Streptococcus pneumoniae

U2 - 10.1111/j.1462-5822.2010.01490.x

DO - 10.1111/j.1462-5822.2010.01490.x

M3 - Article

C2 - 20557315

VL - 12

SP - 1576

EP - 1588

JO - Cellular Microbiology

JF - Cellular Microbiology

SN - 1462-5814

IS - 11

ER -