scholarly journals Monocyte Chemoattractant Protein 1 Regulates Pulmonary Host Defense via Neutrophil Recruitment during Escherichia coli Infection

2011 ◽  
Vol 79 (7) ◽  
pp. 2567-2577 ◽  
Author(s):  
Gayathriy Balamayooran ◽  
Sanjay Batra ◽  
Theivanthiran Balamayooran ◽  
Shanshan Cai ◽  
Samithamby Jeyaseelan
Keyword(s):  
Escherichia Coli ◽  
Host Defense ◽  
Neutrophil Recruitment ◽  
Bacterial Clearance ◽  
Content Type ◽  
Monocyte Chemoattractant Protein 1 ◽  
Neutrophil Influx ◽  
E Coli ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

ABSTRACTNeutrophil accumulation is a critical event to clear bacteria. Since uncontrolled neutrophil recruitment can cause severe lung damage, understanding neutrophil trafficking mechanisms is important to attenuate neutrophil-mediated damage. While monocyte chemoattractant protein 1 (MCP-1) is known to be a monocyte chemoattractant, its role in pulmonary neutrophil-mediated host defense against Gram-negative bacterial infection is not understood. We hypothesized that MCP-1/chemokine (C-C motif) ligand 2 is important for neutrophil-mediated host defense. Reduced bacterial clearance in the lungs was observed in MCP-1−/−mice followingEscherichia coliinfection. Neutrophil influx, along with cytokines/chemokines, leukotriene B4(LTB4), and vascular cell adhesion molecule 1 levels in the lungs, was reduced in MCP-1−/−mice after infection.E. coli-induced activation of NF-κB and mitogen-activated protein kinases in the lung was also reduced in MCP-1−/−mice. Administration of intratracheal recombinant MCP-1 (rMCP-1) to MCP-1−/−mice induced pulmonary neutrophil influx and cytokine/chemokine responses in the presence or absence ofE. coliinfection. Ourin vitromigration experiment demonstrates MCP-1-mediated neutrophil chemotaxis. Notably, chemokine receptor 2 is expressed on lung and blood neutrophils, which are increased uponE. coliinfection. Furthermore, our findings show that neutrophil depletion impairsE. coliclearance and that exogenous rMCP-1 after infection improves bacterial clearance in the lungs. Overall, these new findings demonstrate thatE. coli-induced MCP-1 causes neutrophil recruitment directly via chemotaxis as well as indirectly via modulation of keratinocyte cell-derived chemokine, macrophage inflammatory protein 2, and LTB4.

scholarly journals Bacterial Dose-Dependent Role of G Protein-Coupled Receptor Kinase 5 in Escherichia coli-Induced Pneumonia

2016 ◽  
Vol 84 (5) ◽  
pp. 1633-1641 ◽  
Author(s):  
Nandakumar Packiriswamy ◽  
Michael Steury ◽  
Ian C. McCabe ◽  
Scott D. Fitzgerald ◽  
Narayanan Parameswaran
Keyword(s):  
Escherichia Coli ◽  
G Protein ◽  
Lethal Dose ◽  
Neutrophil Recruitment ◽  
Sublethal Dose ◽  
Receptor Kinase ◽  
Content Type ◽  
E Coli ◽  
G Protein Coupled

G protein-coupled receptor kinase 5 (GRK5) is a serine/threonine kinase previously shown to mediate polymicrobial sepsis-induced inflammation. The goal of the present study was to examine the role of GRK5 in monomicrobial pulmonary infection by using an intratrachealEscherichia coliinfection model of pneumonia. We used sublethal and lethal doses ofE. colito examine the mechanistic differences between low-grade and high-grade inflammation induced byE. coliinfection. With a sublethal dose ofE. coli, GRK5 knockout (KO) mice exhibited higher plasma CXCL1/KC levels and enhanced lung neutrophil recruitment early after infection, and lower bacterial loads, than wild-type (WT) mice. The inflammatory response was also diminished, and resolution of inflammation advanced, in the lungs of GRK5 KO mice. In contrast to the reduced bacterial loads in GRK5 KO mice following a sublethal dose, at a lethal dose ofE. coli, the bacterial burdens remained high in GRK5 KO mice relative to those in WT mice. This occurred in spite of enhanced plasma CXCL1 levels as well as neutrophil recruitment in the KO mice. But the recruited neutrophils (following high-dose infection) exhibited decreased CD11b expression and reduced reactive oxygen species production, suggesting decreased neutrophil activation or increased neutrophil exhaustion in the GRK5 KO mice. In agreement with the increased bacterial burden, KO mice showed poorer survival than WT mice followingE. coliinfection at a lethal dose. Overall, our data suggest that GRK5 negatively regulates CXCL1/KC levels during bacterial pneumonia but that the role of GRK5 in the clinical outcome in this model is dependent on the bacterial dose.

scholarly journals Role of Toll-like receptor 5 in the innate immune response to acute P. aeruginosa pneumonia

2009 ◽  
Vol 297 (6) ◽  
pp. L1112-L1119 ◽  
Author(s):  
Amy E. Morris ◽  
H. Denny Liggitt ◽  
Thomas R. Hawn ◽  
Shawn J. Skerrett
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Bacterial Clearance ◽  
Toll Like Receptor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
High Inoculum ◽  
Toll Like Receptor 5

Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and an important pathogen in patients with chronic lung disease, such as cystic fibrosis and bronchiectasis. The contribution of Toll-like receptor 5 (TLR5) to the innate immune response to this organism is incompletely understood. We exposed wild-type and TLR5-deficient ( Tlr5−/−) mice to aerosolized P. aeruginosa at low and high inocula and assessed bacterial clearance, lung inflammation, and cytokine production 4 and 24 h after infection. Bacterial clearance was impaired in Tlr5−/−mice after low-inoculum, but not high-inoculum, infection. Early bronchoalveolar accumulation of neutrophils was reduced in Tlr5−/−mice after low- and high-dose infection. Cytokine responses, including markedly impaired monocyte chemoattractant protein-1 production 4 h after low- and high-inoculum challenge, were selectively altered in Tlr5−/−mice. In contrast, there was no impairment of bacterial clearance, neutrophil recruitment, or monocyte chemoattractant protein-1 production in Tlr5−/−mice after infection with a nonflagellated isotypic strain of P. aeruginosa . Thus TLR5-mediated recognition of flagellin is involved in activating pulmonary defenses against P. aeruginosa and contributes to antibacterial resistance in a manner that is partially inoculum dependent. These data are the first to demonstrate a unique role for TLR5 in the innate immune response to P. aeruginosa lung infection.

Expression of monocyte chemoattractant protein-1 in meningioma

1995 ◽  
Vol 82 (5) ◽  
pp. 874-878 ◽  
Author(s):  
Kyoichi Sato ◽  
Jun-Ichi Kuratsu ◽  
Hideo Takeshima ◽  
Teizo Yoshimura ◽  
Yukitaka Ushio
Keyword(s):  
Culture Fluid ◽  
Glioma Cell Line ◽  
Macrophage Infiltration ◽  
Content Type ◽  
Monocyte Chemoattractant Protein 1 ◽  
Messenger Ribonucleic Acid ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Perifocal Edema ◽  
Fine Print

✓ Monocyte chemoattractant protein-1 (MCP-1), purified from glioma cell line (U-105MG) culture fluid, attracts monocytes but not neutrophils. Macrophage accumulation is one of the pathological features of meningioma. To investigate the mechanism of macrophage infiltration into meningioma, the expression and localization of MCP-1 in 16 cases of meningioma were studied using Northern blot analysis and immunohistochemistry. Seven of 16 meningiomas expressed MCP-1 messenger ribonucleic acid and protein, and some degree of macrophage infiltration was seen in all 16 meningiomas. There was a relationship between MCP-1 expression and the degree of macrophage infiltration; MCP-1 was strongly expressed in meningiomas with a high degree of macrophage infiltration. Sometimes the meningioma was accompanied by perifocal edema; a correlation between macrophage infiltration into brain tumors and perifocal edema has already been reported. It was found that the degree of MCP-1 expression is not correlated with the extent of perifocal edema. The authors' findings suggest that MCP-1 plays an important role in macrophage infiltration into meningioma.

scholarly journals Role of Host Xanthine Oxidase in Infection Due to Enteropathogenic and Shiga-Toxigenic Escherichia coli

2013 ◽  
Vol 81 (4) ◽  
pp. 1129-1139 ◽  
Author(s):  
John K. Crane ◽  
Tonniele M. Naeher ◽  
Jacqueline E. Broome ◽  
Edgar C. Boedeker
Keyword(s):  
Escherichia Coli ◽  
Xanthine Oxidase ◽  
Host Defense ◽  
Pathogenic Bacteria ◽  
Intestinal Cell ◽  
Intestinal Loop ◽  
Loop Model ◽  
Content Type ◽  
E Coli

ABSTRACTXanthine oxidase (XO), also known as xanthine oxidoreductase, has long been considered an important host defense molecule in the intestine and in breastfed infants. Here, we present evidence that XO is released from and active in intestinal tissues and fluids in response to infection with enteropathogenicEscherichia coli(EPEC) and Shiga-toxigenicE. coli(STEC), also known as enterohemorrhagicE. coli(EHEC). XO is released into intestinal fluids in EPEC and STEC infection in a rabbit animal model. XO activity results in the generation of surprisingly high concentrations of uric acid in both cultured cell and animal models of infection. Hydrogen peroxide (H2O2) generated by XO activity triggered a chloride secretory response in intestinal cell monolayers within minutes but decreased transepithelial electrical resistance at 6 to 22 h. H2O2generated by XO activity was effective at killing laboratory strains ofE. coli, commensal microbiotas, and anaerobes, but wild-type EPEC and STEC strains were 100 to 1,000 times more resistant to killing or growth inhibition by this pathway. Instead of killing pathogenic bacteria, physiologic concentrations of XO increased virulence by inducing the production of Shiga toxins from STEC strains.In vivo, exogenous XO plus the substrate hypoxanthine did not protect and instead worsened the outcome of STEC infection in the rabbit ligated intestinal loop model of infection. XO released during EPEC and STEC infection may serve as a virulence-inducing signal to the pathogen and not solely as a protective host defense.

scholarly journals Subtilase Cytotoxin Enhances Escherichia coli Survival in Macrophages by Suppression of Nitric Oxide Production through the Inhibition of NF-κB Activation

2012 ◽  
Vol 80 (11) ◽  
pp. 3939-3951 ◽  
Author(s):  
Hiroyasu Tsutsuki ◽  
Kinnosuke Yahiro ◽  
Kotaro Suzuki ◽  
Akira Suto ◽  
Kohei Ogura ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Escherichia Coli ◽  
Inos Expression ◽  
Inos Mrna ◽  
No Production ◽  
Content Type ◽  
Monocyte Chemoattractant Protein 1 ◽  
E Coli ◽  
Inos Promoter ◽  
Subtilase Cytotoxin

ABSTRACTSubtilase cytotoxin (SubAB), which is produced by certain strains of Shiga-toxigenicEscherichia coli(STEC), cleaves an endoplasmic reticulum (ER) chaperone, BiP/Grp78, leading to induction of ER stress and caspase-dependent apoptosis. SubAB alters the innate immune response. SubAB pretreatment of macrophages inhibited lipopolysaccharide (LPS)-induced production of both monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor α (TNF-α). We investigated here the mechanism by which SubAB inhibits nitric oxide (NO) production by mouse macrophages. SubAB suppressed LPS-induced NO production through inhibition of inducible NO synthase (iNOS) mRNA and protein expression. Further, SubAB inhibited LPS-induced IκB-α phosphorylation and nuclear localization of the nuclear factor-κB (NF-κB) p65/p50 heterodimer. Reporter gene and chromatin immunoprecipitation (ChIP) assays revealed that SubAB reduced LPS-induced NF-κB p65/p50 heterodimer binding to an NF-κB binding site on the iNOS promoter. In contrast to the native toxin, a catalytically inactivated SubAB mutant slightly enhanced LPS-induced iNOS expression and binding of NF-κB subunits to the iNOS promoter. The SubAB effect on LPS-induced iNOS expression was significantly reduced in macrophages from NF-κB1 (p50)-deficient mice, which lacked a DNA-binding subunit of the p65/p50 heterodimer, suggesting that p50 was involved in SubAB-mediated inhibition of iNOS expression. Treatment of macrophages with an NOS inhibitor or expression of SubAB byE. coliincreasedE. colisurvival in macrophages, suggesting that NO generated by macrophages resulted in efficient killing of the bacteria and SubAB contributed toE. colisurvival in macrophages. Thus, we hypothesize that SubAB might represent a novel bacterial strategy to circumvent host defense during STEC infection.

scholarly journals NOD2 Signaling Contributes to Host Defense in the Lungs against Escherichia coli Infection

2012 ◽  
Vol 80 (7) ◽  
pp. 2558-2569 ◽  
Author(s):  
Balamayooran Theivanthiran ◽  
Sanjay Batra ◽  
Gayathriy Balamayooran ◽  
Shanshan Cai ◽  
Koichi Kobayashi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Host Defense ◽  
The United States ◽  
Bacterial Burden ◽  
Bacterial Killing ◽  
Ligand Interaction ◽  
Chemokine Production ◽  
Content Type ◽  
E Coli

ABSTRACTBacterial pneumonia remains a significant cause of mortality in the United States. The innate immune response is the first line of defense against invading bacteria. Neutrophil recruitment to the lungs is the first step in a multistep sequence leading to bacterial clearance. Ligand interaction with pattern-recognizing receptors (PRRs) leads to chemokine production, which drives neutrophils to the site of infection. Although we demonstrated that RIP2 is important for host defense in the lungs againstEscherichia coli, the individual roles of NOD1 and NOD2 in pulmonary defense have not been addressed. Here, we explored the role of NOD2 in neutrophil-mediated host defense against an extracellular pathogen,E. coli. We found enhanced bacterial burden and reduced neutrophil and cytokine/chemokine levels in the lungs of NOD2−/−mice followingE. coliinfection. Furthermore, we observed reduced activation of NF-κB and mitogen-activated protein kinases (MAPKs) in the lungs of NOD2−/−mice uponE. colichallenge. Moreover, NOD2−/−neutrophils show impaired intracellular bacterial killing. Using NOD2/RIP2−/−mice, we observed bacterial burden and neutrophil accumulation in the lungs similar to those seen with NOD2−/−mice. In addition, bone marrow-derived macrophages obtained from NOD2/RIP2−/−mice demonstrate a reduction in activation of NF-κB and MAPKs similar to that seen with NOD2−/−mice in response toE. coli. These findings unveil a previously unrecognized role of the NOD2-RIP2 axis for host defense against extracellular Gram-negative bacteria. This pathway may represent a novel target for the treatment of lung infection/inflammation.

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