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Mark C Dessing,
Wilco P Pulskens,
Gwendoline J Teske,
Loes M Butter,
Tom van der Poll,
Huan Yang,
Kevin J Tracey,
Peter P Nawroth,
Angelika Bierhaus,
Sandrine Florquin,
Jaklien C Leemans
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ABSTRACT: The receptor for advanced glycation end products (RAGE) mediates a variety of inflammatory responses in renal diseases, but its role in renal ischemia/reperfusion (I/R) injury is unknown. We showed that during renal I/R, RAGE ligands HMGB1 and S100B are expressed. However, RAGE deficiency does not affect renal injury and function upon I/R-induced injury.
Journal of Innate Immunity 11/2011; 4(1):80-5. · 4.21 Impact Factor
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ABSTRACT: Interleukin (IL)-15 is a cytokine that has a broad tissue distribution and is important in maintaining homeostasis of cells and stability of tissues. When II-15 is also expressed by vascular smooth muscle cells (SMC), which are the dominant type of cells in most atherosclerotic plaques, it could be important in maintaining plaque tissue integrity and hence resistance of plaques towards development of clinically relevant complications such as plaque rupture and thrombosis. In this study, IL-15 and IL-15Rα in vitro expression by coronary artery SMC was investigated using RT -PCR and FACS analysis. Immunohistochemistry was used to study in situ expression of IL-15 and IL-15R by SMC of human carotid artery atherosclerotic plaques. Multiplex ligand-dependent probe amplification (MLPA) was used to investigate the mRNA expression of 40 pro- and anti inflammatory genes after stimulating coronary SMC with IL-15. We found that atherosclerotic SMC express both IL-15 and its receptor IL-15R, and TNF-γ and TNF-α enhance IL-15R expression in cultured SMC. MLPA studies on SMC revealed enhanced expression of PDGF beta mRNA after IL15 stimulation. In conclusion, our data suggest that IL-15 may contribute to atherosclerotic plaque integrity by stimulation of smooth muscle cells, probably in a PDGF dependent fashion.
International journal of clinical and experimental pathology 03/2011; 4(3):287-94. · 1.89 Impact Factor
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ABSTRACT: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or β-catenin causes constitutively active β-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the Apc(Min/+) mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of β-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which uncontrolled epithelial cell proliferation in the stem cell compartment can be counterbalanced by an increased propensity to undergo cell death.
Biochemical and Biophysical Research Communications 12/2010; 406(1):1-6. · 2.48 Impact Factor
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ABSTRACT: Experimental studies have shown potential for Toll-like receptor (TLR) profiling in renal allograft in predicting renal outcome after transplantation. Our goal was to determine if profiling of TLR1-10 and TLR-related genes could be used as a prognostic value for renal function and late clinical outcome after transplantation.
TLR1-10, CD14, MD-2 and negative regulators Toll-interacting protein (TOLLIP) and single immunoglobulin domain IL-1R-related receptor were analysed in 36 biopsies from renal transplant recipients with acute rejection (AR) and in 14 biopsies from renal transplant recipients without rejection (NR). Analysis was performed by multiplex ligation-dependent probe amplification. TLR (-related) genes were correlated to Banff'07 classification, cellular influx, response to conventional anti-rejection therapy, renal function 12 and 24 months after rejection and graft loss.
mRNA levels of most TLRs were significantly higher in acute rejection while TOLLIP mRNA level was decreased. mRNA levels of TLR1/2/4/7/8 were highly accurate in distinguishing AR from NR. TLR mRNA levels correlated to inflammatory parameters according to the Banff'07 classification and to cellular influx. Elevated mRNA level of TLR3 in acute rejection was independent from infiltrating leukocytes. TLR (-related) genes were not correlated with response to conventional anti-rejection therapy. Splice variant TLR4r3 was associated with poor renal function 24 months after transplantation, and TLR1 appeared to be associated with graft loss.
The elevated mRNA levels of several TLRs in association with reduced mRNA levels of TOLLIP in renal transplant biopsies of patients with acute rejection indicate a pro-inflammatory state, which may contribute to uncontrolled inflammation.
Nephrology Dialysis Transplantation 09/2010; 25(12):4087-92. · 3.40 Impact Factor
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ABSTRACT: Inflammation is commonly followed by the release of endogenous proteins called danger associated molecular patterns (DAMPs) that are able to warn the host for eminent danger. S100A8/A9 subunits are DAMPs that belong to the S100 family of calcium binding proteins. S100A8/A9 complexes induce an inflammatory response and their expression correlates with disease severity in several inflammatory disorders. S100A8/A9 promote endotoxin- and Escherichia (E.) coli-induced sepsis showing its contribution in systemic infection. The role of S100A8/A9 during a local infection of the urinary tract system caused by E. coli remains unknown.
We investigated the contribution of S100A8/A9 in acute urinary tract infection (UTI) by instilling 2 different doses of uropathogenic E. coli transurethrally in wild type (WT) and S100A9 knockout (KO) mice. Subsequently, we determined bacterial outgrowth, neutrophilic infiltrate and inflammatory mediators in bladder and kidney 24 and 48 hours later. UTI resulted in a substantial increase of S100A8/A9 protein in bladder and kidney tissue of WT mice. S100A9 KO mice displayed similar bacterial load in bladder or kidney homogenate compared to WT mice using 2 different doses at 2 different time points. S100A9 deficiency had little effect on the inflammatory responses to E. Coli-induced UTI infection, as assessed by myeloperoxidase activity in bladder and kidneys, histopathologic analysis, and renal and bladder cytokine concentrations.
We show that despite high S100A8/A9 expression in bladder and kidney tissue upon UTI, S100A8/A9 does not contribute to an effective host response against E. Coli in the urinary tract system.
PLoS ONE 01/2010; 5(10):e13394. · 4.09 Impact Factor
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ABSTRACT: Many in vitro studies have focused on gene expression in influenza-infected leukocytes, lung tissue or cell lines. However, knowledge of in vivo gene expression in these compartments is limited.
To obtain insight into gene expression profiles during influenza infection, we determined the expression of multiple genes by using a newly developed mouse-specific multiplex ligation-dependent probe amplification assay.
The genes involved in inflammation, Toll-like receptor signaling, coagulation, fibrinolysis, cell adhesion, tissue repair and homeostasis were measured in lung tissue, leukocytes in bronchoalveolar lavage fluid and tracheal epithelial cells in mice, before and after intranasal infection with influenza A. Most of the genes investigated were differentially expressed during the course of infection and returned to baseline levels when mice had recovered from the infection. However, expression of several genes remained altered even though mice had completely cleared the virus.
These data provide the first information on compartmentalized gene expression profiles in the respiratory tract during influenza.
Journal of Innate Immunity 01/2009; 1(4):366-75. · 4.21 Impact Factor
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ABSTRACT: Pneumolysin (PLN) is an intracellular toxin of Streptococcus pneumoniae that has been implicated as a major virulence factor in infections caused by this pathogen. Conserved bacterial motifs are recognized by the immune system by pattern recognition receptors among which the family of Toll-like receptors (TLRs) prominently features. The primary objective of the present study was to determine the role of TLR2 and TLR4 in lung inflammation induced by intrapulmonary delivery of PLN.
First, we confirmed that purified PLN activates cells via TLR4 (not via TLR2) in vitro, using human embryonic kidney cells transfected with either TLR2 or TLR4. Intranasal administration of PLN induced an inflammatory response in the pulmonary compartment of mice in vivo, as reflected by influx of neutrophils, release of proinflammatory cytokines and chemokines, and a rise in total protein concentrations in bronchoalveolar lavage fluid. These PLN-induced responses were dependent in part, not only on TLR4, but also on TLR2, as indicated by studies using TLR deficient mice.
These data suggest that although purified PLN is recognized by TLR4 in vitro, PLN elicits lung inflammation in vivo by mechanisms that may involve multiple TLRs.
PLoS ONE 01/2009; 4(11):e7993. · 4.09 Impact Factor
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ABSTRACT: Melioidosis, caused by the bacterium Burkholderia pseudomallei, is a septicemic illness, often associated with pneumonia and bacterial dissemination to distant sites. Recently we reported the inflammatory mRNA profile in blood leukocytes during human melioidosis. Knowledge of the inflammatory gene expression profile in the pulmonary compartment after infection with B. pseudomallei, however, is highly limited. We therefore aimed to characterize the inflammatory mRNA profile in the pulmonary and systemic compartment during murine melioidosis. By using a newly developed mouse specific Multiplex-Ligation-dependent-Probe-Amplification (MLPA) assay we determined the expression profile of 33 genes encoding inflammatory proteins in lung tissue, leukocytes in bronchoalveolar-lavage-fluid (BALF) and blood leukocytes in mice before and at several time points after intranasal infection with B. pseudomallei. Relative to naïve mice, mice intranasally infected with B. pseudomallei showed increased transcription of a whole array of genes involved in inflammation, Toll-like receptor-signaling, coagulation, fibrinolysis, cell adhesion, tissue repair and homeostasis in the lung, BALF and blood compartment. Notably, many inflammatory genes were shown to be differentially expressed during the course of infection. These data provide new information on compartmentalized inflammatory gene-expression profiles after infection with B. pseudomallei, increasing our insights into the extent of inflammation activation in the pulmonary and systemic compartment during melioidosis.
Microbes and Infection 07/2008; 10(8):868-77. · 3.10 Impact Factor
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ABSTRACT: Beta2-adrenergic receptors are expressed on different cell types in the lung, including respiratory epithelial cells, smooth muscle cells, and macrophages. The aim of the current study was to determine the role of beta-adrenergic receptors in the regulation of lung inflammation induced by instillation via the airways of lipopolysaccharide (LPS) (a constituent of the gram-negative bacterial cell wall) or lipoteichoic acid (LTA) (a component of the gram-positive bacterial cell wall). Mice inhaled the beta-adrenergic antagonist propranolol or saline 30 minutes before and 3 hours after intranasal LPS or LTA administration. LPS and LTA induced a profound inflammatory response in the lungs as reflected by an influx of neutrophils and the release of proinflammatory cytokines and chemokines into bronchoalveolar lavage fluid (BALF). Propranolol inhalation resulted in enhanced LPS-induced lung inflammation, which was reflected by a stronger secretion of TNF-alpha, IL-6, and monocyte chemoattractant protein-1 into BALF and by enhanced coagulation activation (thrombin-antithrombin complexes). In LTA-induced lung inflammation, propranolol did not influence cytokine release but potentiated activation of coagulation. Propranolol did not alter neutrophil recruitment in either model. This study suggests that beta-adrenergic receptors, which are widely expressed in the lungs, serve as negative regulators of pulmonary cytokine release and coagulation induced by LPS and less so during LTA-induced pulmonary inflammation.
American Journal of Respiratory Cell and Molecular Biology 05/2008; 39(3):373-9. · 5.13 Impact Factor
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ABSTRACT: The cell wall of Streptococcus pneumoniae consists of lipoteichoic acid (LTA), which is released when pneumococci are killed by either the host immune system or antibiotic treatment. Release of excessive amounts of LTA has been implicated in the toxic sequelae of severe gram-positive infection by virtue of its proinflammatory properties. Several in vitro studies have shown that LTA is recognized by Toll-like receptor (TLR) 2 and CD14. Our objective here was to investigate the inflammatory properties of S. pneumoniae LTA in vivo and the role played by TLR2, TLR4, and CD14 therein.
Wild-type (WT), TLR2 knockout (KO), TLR4 KO, TLR2x4 double-KO, and CD14 KO mice were intranasally inoculated with highly purified pneumococcal LTA.
LTA induced a dose-dependent inflammatory response and activation of the coagulation and fibrinolytic pathways in a TLR2-dependent fashion. Surprisingly, TLR4 KO mice also displayed a somewhat diminished pulmonary inflammatory and coagulant response compared with WT mice, possibly as a result of absent TLR4 signaling through LTA-induced release of endogenous mediators.
Pneumococcal LTA induces a profound inflammatory response and activation of the coagulation pathway in the lungs in vivo through a TLR2-dependent route, which likely is amplified by endogenous TLR4 ligands.
The Journal of Infectious Diseases 02/2008; 197(2):245-52. · 6.41 Impact Factor
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ABSTRACT: Mechanical ventilation with high tidal volumes aggravates lung injury in patients with acute lung injury or acute respiratory distress syndrome. The authors sought to determine the effects of short-term mechanical ventilation on local inflammatory responses in patients without preexisting lung injury.
Patients scheduled to undergo an elective surgical procedure (lasting > or = 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h thereafter, bronchoalveolar lavage fluid and/or blood was investigated for polymorphonuclear cell influx, changes in levels of inflammatory markers, and nucleosomes.
Mechanical ventilation with lower tidal volumes and PEEP (n = 21) attenuated the increase of pulmonary levels of interleukin (IL)-8, myeloperoxidase, and elastase as seen with higher tidal volumes and no PEEP (n = 19). Only for myeloperoxidase, a difference was found between the two ventilation strategies after 5 h of mechanical ventilation (P < 0.01). Levels of tumor necrosis factor alpha, IL-1alpha, IL-1beta, IL-6, macrophage inflammatory protein 1alpha, and macrophage inflammatory protein 1beta in the bronchoalveolar lavage fluid were not affected by mechanical ventilation. Plasma levels of IL-6 and IL-8 increased with mechanical ventilation, but there were no differences between the two ventilation groups.
The use of lower tidal volumes and PEEP may limit pulmonary inflammation in mechanically ventilated patients without preexisting lung injury. The specific contribution of both lower tidal volumes and PEEP on the protective effects of the lung should be further investigated.
Anesthesiology 02/2008; 108(1):46-54. · 5.36 Impact Factor
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ABSTRACT: Toll-like receptors (TLRs) are pattern recognition receptors that recognize conserved molecular patterns expressed by pathogens. Pneumolysin, an intracellular toxin found in all Streptococcus pneumoniae clinical isolates, is an important virulence factor of the pneumococcus that is recognized by TLR4. Although TLR2 is considered the most important receptor for Gram-positive bacteria, our laboratory previously could not demonstrate a decisive role for TLR2 in host defence against pneumonia caused by a serotype 3 S. pneumoniae. Here we tested the hypothesis that in the absence of TLR2, S. pneumoniae can still be sensed by the immune system through an interaction between pneumolysin and TLR4. C57BL/6 wild-type (WT) and TLR2 knockout (KO) mice were intranasally infected with either WT S. pneumoniae D39 (serotype 2) or the isogenic pneumolysin-deficient S. pneumoniae strain D39 PLN. TLR2 did not contribute to antibacterial defence against WT S. pneumoniae D39. In contrast, pneumolysin-deficient S. pneumoniae only grew in lungs of TLR2 KO mice. TLR2 KO mice displayed a strongly reduced early inflammatory response in their lungs during pneumonia caused by both pneumolysin-producing and pneumolysin-deficient pneumococci. These data suggest that pneumolysin-induced TLR4 signalling can compensate for TLR2 deficiency during respiratory tract infection with S. pneumoniae.
Cellular Microbiology 02/2008; 10(1):237-46. · 5.46 Impact Factor
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ABSTRACT: Monocyte chemoattractant protein 1 (MCP-1) and its receptor CCR2 have been shown to play an import role in leukocyte recruitment to sites of infection and inflammation. To investigate the role of MCP-1 during infection with influenza we inoculated wild-type (WT) and MCP-1 knockout (KO) mice with a non-lethal dose of a mouse adapted strain of influenza A. Influenza infection of WT mice resulted in a profound increase in pulmonary MCP-1 levels. MCP-1 KO mice had enhanced weight loss and did not fully regain their body weight during the 14-day observation period. In addition, MCP-1 KO mice demonstrated elevated viral loads 8 days after infection, which was accompanied by reduced leukocyte recruitment into the infected lungs, primarily caused by a diminished influx of macrophages and granulocytes. Moreover, pulmonary levels of IgA were reduced in MCP-1 KO mice. The pulmonary concentrations of tumor necrosis factor-alpha, interleukin-6, macrophage inflammatory protein 2 and interferon-gamma were higher in MCP-1 KO mice. This study shows that MCP-1 contributes to an adequate protective immune response against influenza infection in mice.
Clinical Immunology 01/2008; 125(3):328-36. · 4.05 Impact Factor
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ABSTRACT: Background: Mechanical ventilation with high tidal volumes aggravates lung injury in patients with acute lung injury or acute respiratory distress syndrome. The authors sought to determine the effects of short-term mechanical ventilation on local inflammatory responses in patients without preexisting lung injury.
Anesthesiology 12/2007; 108(1):46-54. · 5.36 Impact Factor
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ABSTRACT: Influenza A is a single stranded (ss)RNA virus that can cause upper respiratory tract infections that in rare cases may progress to pneumonia. Toll-like receptors (TLRs) and CD14 are receptors which recognize viral proteins and nucleic acid of several viruses. CD14 is required for influenza-induced cytokine production during infection of mouse macrophages. In addition, CD14 was shown to bind ssRNA, suggesting an important role for CD14 during infection with influenza. To investigate the role of CD14 during influenza pneumonia we inoculated WT and CD14 KO mice with a non-lethal dose of a mouse adapted strain of influenza A. CD14 KO mice displayed a reduced viral load in the lungs, 2 and 14 days after infection with influenza. Pulmonary cytokine production in CD14 KO mice was reduced at day 2 and elevated at day 8 compared to WT mice. CD14 deficiency did not influence lymphocyte recruitment or lymphocyte activation in lungs and draining lymph nodes 8 days after infection. These data show that CD14 plays a limited role in host defense against infection with influenza.
Immunology Letters 11/2007; 113(1):47-51. · 2.53 Impact Factor
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W Joost Wiersinga,
Catharina W Wieland, Mark C Dessing,
Narisara Chantratita,
Allen C Cheng,
Direk Limmathurotsakul,
Wirongrong Chierakul,
Masja Leendertse,
Sandrine Florquin,
Alex F de Vos,
Nicholas White,
Arjen M Dondorp,
Nicholas P Day,
Sharon J Peacock,
Tom van der Poll
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ABSTRACT: Toll-like receptors (TLRs) are essential in host defense against pathogens by virtue of their capacity to detect microbes and initiate the immune response. TLR2 is seen as the most important receptor for gram-positive bacteria, while TLR4 is regarded as the gram-negative TLR. Melioidosis is a severe infection caused by the gram-negative bacterium, Burkholderia pseudomallei, that is endemic in Southeast Asia. We aimed to characterize the expression and function of TLRs in septic melioidosis.
Patient studies: 34 patients with melioidosis demonstrated increased expression of CD14, TLR1, TLR2, and TLR4 on the cell surfaces of monocytes and granulocytes, and increased CD14, TLR1, TLR2, TLR4, LY96 (also known as MD-2), TLR5, and TLR10 mRNA levels in purified monocytes and granulocytes when compared with healthy controls. In vitro experiments: Whole-blood and alveolar macrophages obtained from TLR2 and TLR4 knockout (KO) mice were less responsive to B. pseudomallei in vitro, whereas in the reverse experiment, transfection of HEK293 cells with either TLR2 or TLR4 rendered these cells responsive to this bacterium. In addition, the lipopolysaccharide (LPS) of B. pseudomallei signals through TLR2 and not through TLR4. Mouse studies: Surprisingly, TLR4 KO mice were indistinguishable from wild-type mice with respect to bacterial outgrowth and survival in experimentally induced melioidosis. In contrast, TLR2 KO mice displayed a markedly improved host defenses as reflected by a strong survival advantage together with decreased bacterial loads, reduced lung inflammation, and less distant-organ injury.
Patients with melioidosis displayed an up-regulation of multiple TLRs in peripheral blood monocytes and granulocytes. Although both TLR2 and TLR4 contribute to cellular responsiveness to B. pseudomallei in vitro, TLR2 detects the LPS of B. pseudomallei, and only TLR2 impacts on the immune response of the intact host in vivo. Inhibition of TLR2 may be a novel treatment strategy in melioidosis.
PLoS Medicine 08/2007; 4(7):e248. · 16.27 Impact Factor
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ABSTRACT: Sepsis is characterized by an uncontrolled inflammatory response to invading microorganisms. We describe the inflammatory mRNA profiles in whole-blood leukocytes, monocytes, and granulocytes using a multigene system for 35 inflammatory markers that included pro- and anti-inflammatory cytokines, chemokines, and signal transduction molecules in a case-control study with 34 patients with sepsis caused by the gram-negative bacterium Burkholderia pseudomallei (the pathogen causing melioidosis) and 32 healthy volunteers. Relative to healthy controls, patients with sepsis showed increased transcription of a whole array of inflammatory genes in peripheral blood leukocytes, granulocytes, and monocytes. Specific monocyte and granulocyte mRNA profiles were identified. Strong correlations were found between inflammatory mRNA expression levels in monocytes and clinical outcome. These data underline the notion that circulating leukocytes are an important source for inflammatory mediators in patients with gram-negative sepsis. Gene profiling such as was done here provides an excellent tool to obtain insight into the extent of inflammation activation in patients with severe infection.
Infection and Immunity 07/2007; 75(6):3074-9. · 4.16 Impact Factor
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ABSTRACT: Influenza A can be complicated by secondary bacterial pneumonia, which is most frequently caused by Streptococcus pneumoniae and associated with uncontrolled pulmonary inflammation. Evidence points to Toll-like receptor (TLR) 2 as a possible mediator of this exaggerated lung inflammation: (1) TLR2 is the most important "sensor" for gram-positive stimuli, (2) TLR2 contributes to S. pneumoniae-induced inflammation, and (3) influenza A enhances TLR2 expression in various cell types. Therefore, the objective of this study was to determine the role of TLR2 in the host response to postinfluenza pneumococcal pneumonia. TLR2 knockout (KO) and wild-type (WT) mice were infected intranasally with influenza A virus. Fourteen days later they were administered with S. pneumoniae intranasally. Influenza was associated with a similar transient weight loss in TLR2 KO and WT mice. Both mouse strains were fully recovered and had completely cleared the virus at Day 14. Importantly, no differences between TLR2 KO and WT mice were detected during postinfluenza pneumococcal pneumonia with respect to bacterial growth, lung inflammation, or cytokine/chemokine concentrations, with the exception of lower pulmonary levels of cytokine-induced neutrophil chemoattractant in TLR2 KO mice. Toll-like receptor 2 does not contribute to host defense during murine postinfluenza pneumococcal pneumonia.
American Journal of Respiratory Cell and Molecular Biology 06/2007; 36(5):609-14. · 5.13 Impact Factor
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ABSTRACT: CD14 is a pattern recognition receptor that can interact with a variety of bacterial ligands. During gram-negative infection, CD14 plays an important role in the induction of a protective immune response by virtue of its capacity to recognize lipopolysaccharide in the bacterial cell wall. Knowledge of the contribution of CD14 to host defense against gram-positive infections is limited.
To study the role of CD14 in gram-positive bacterial pneumonia.
CD14 knockout (KO) and normal wild-type (WT) mice were intranasally infected with Streptococcus pneumoniae.
CD14 KO mice demonstrated a strongly reduced lethality, which was accompanied by a more than 10-fold lower bacterial load in lung homogenates but not in bronchoalveolar lavage fluid at 48 hours after infection. Strikingly, CD14 KO mice failed to develop positive blood cultures, whereas WT mice had positive blood cultures from 24 hours onward and eventually invariably had evidence of systemic infection. Lung inflammation was attenuated in CD14 KO mice at 48 hours after infection, as evaluated by histopathology and cytokine and chemokine levels. Intrapulmonary delivery of recombinant soluble CD14 to CD14 KO mice rendered them equally susceptible to S. pneumoniae as WT mice, resulting in enhanced bacterial growth in lung homogenates and bacteremia, indicating that the presence of soluble CD14 in the bronchoalveolar compartment is sufficient to cause invasive pneumococcal disease.
These data suggest that S. pneumoniae uses (soluble) CD14 present in the bronchoalveolar space to cause invasive respiratory tract infection.
American Journal of Respiratory and Critical Care Medicine 04/2007; 175(6):604-11. · 11.08 Impact Factor
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ABSTRACT: To determine the role of monocyte chemoattractant protein 1 (MCP-1) during pneumococcal pneumonia, MCP-1 knockout and wild-type mice were infected with Streptococcus pneumoniae. Pulmonary MCP-1 levels were strongly correlated to bacterial loads in wild-type mice. However, MCP-1 knockout and wild-type mice were indistinguishable with respect to bacterial growth, inflammatory responses, and lethality.
Infection and Immunity 01/2007; 74(12):7021-3. · 4.16 Impact Factor
