Pro-inflammatory cytokine and chemokine release by human brain microvascular endothelial cells stimulated by Streptococcus suis serotype 2

Abstract

Streptococcus suis serotype 2 is a world-wide agent of diseases among pigs including meningitis, septicemia and arthritis. This microorganism is also recognized as an important zoonotic agent. The pathogenesis of the meningitis caused by S. suis is poorly understood. We have previously shown that S. suis is able to adhere to human brain microvascular endothelial cells (BMEC), but not to human umbilical vein endothelial cells (HUVEC). The objective of this work was to study the ability of S. suis serotype 2 to induce the release of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1); IL-6 and the chemokines IL-8 and monocyte chemotactic protein-1 (MCP-1) by human BMEC and HUVEC, using a sandwich enzyme-linked immunosorbent assay. S. suis was able to stimulate the production of IL-6, IL-8 and MCP-1 by BMEC but not HUVEC, in a time- and concentration-dependent manner. Bacterial cell wall components were largely responsible for such stimulation. The human and pig origin of strains does not seem to affect the intensity of the response; indeed, a very heterogeneous pattern of cytokine and chemokine production was observed for the different strains tested in this study. In situ production of cytokines and chemokines by BMEC may be the result of specific adhesion of S. suis to this cell type, with several consequences such as increased recruitment of leukocytes and an increase in the blood-brain barrier permeability.

Interactions ofHaemophilus parasuisand its LOS with porcine brain microvascular endothelial cells

“…Along with other cells, BMEC can produce pro-inflammatory cytokines as a result of stimulation by other cytokines (e.g. TNF-, IL-1 ) [7,40] or direct interaction with microbial pathogens [7,39]. The present study demonstrates for the first time that H. parasuis induces the production of IL-8 and IL-6 by PBMEC.…”

Concepts and Mechanisms: Crossing Host Barriers

“…This response was dependent on the GBS b-h/c toxin, the transcriptional regulator of virulence, CovR and PilA expression (Doran et al 2003;Lembo et al 2010;Banerjee et al 2011). Additional in vitro studies with S. pneumoniae, HiB, S. typhimurium, E. coli K1, Streptococcus suis, L. monocytogenes, and N. meningitidis reveal a similar core BMEC transcriptional response that results in the induction of neutrophil signaling pathways (Wilson and Drevets 1998;Vadeboncoeur et al 2003;Galanakis et al 2006;Schubert-Unkmeir et al 2007;Banerjee et al 2010;van Sorge et al 2011). Continued exposure and invasion of the pathogen may result in overactivation of BBB endothelium and lead to increased inflammation that may ultimately compromise BBB integrity.…”

Streptococcus suisMeningitis, United States

“…The remaining 1 is from Japan and assigned to ST28 (8). Unlike in previous reports, 80% of the human clinical isolates (16 isolates) characterized in this study were assigned to the ST27 complex.…”

“…Once bloodborne, S. suis can cause toxic shock syndrome and sepsis (7). The mechanism by which the organism traverses the bloodbrain barrier to cause meningitis is not known, although bacterial toxins and host infl ammatory mediators may play a role (8).…”