Blocking TREM-1 signaling prolongs survival of mice with Pseudomonas aeruginosa induced sepsis

Wang, Feng; Liu, Shuanglin; Wu, Shiji; Zhu, Qin; Ou, Guoping; Liu, Cailin; Wang, Yue; Liao, Yalong; Sun, Ziyong

doi:10.1016/j.cellimm.2011.10.006

Cited by 51 publications

(69 citation statements)

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“…To evaluate the effect of TREM-1 signaling on the outcome of S. suis infection, we used the recombinant extracellular domain of TREM-1 as an inhibitor and use the agonistic TREM-1 antibody as an activator of signaling, as described previously (33,34,39). PBS and isotype antibody were used as negative controls, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…It can be induced at high levels on neutrophils and monocytes and further amplifies Toll-like receptor (TLR)-initiated responses against microbial challenges, potentiating the secretion of proinflammatory cytokines and chemokines with the help of the DAP12 adaptor protein in response to bacterial and fungal infections (30)(31)(32). Blockage of TREM-1 signaling could protect mice against lipopolysaccharide (LPS)-induced shock and microbial sepsis caused by live Escherichia coli and Pseu-domonas aeruginosa, as well as cecal ligation and puncture (30,33,34). Therefore, TREM-1 has been recognized as an essential regulator of innate immunity in sepsis syndrome and as a potential therapeutic target for septic shock (35).…”

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confidence: 99%

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TREM-1 Signaling Promotes Host Defense during the Early Stage of Infection with Highly Pathogenic Streptococcus suis

et al. 2015

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c Infection with highly pathogenic Streptococcus suis can cause septic shock, which is characterized by high levels of inflammatory cytokines and a high mortality rate. Our previous study indicated that TREM-1 (triggering receptor expressed on myeloid cells 1) was upregulated in swine spleen cells in response to S. suis infection. The role of TREM-1 signaling in enhancement of the proinflammatory response promoted us to examine its effect on the outcome of S. suis infection. In the present study, the recombinant extracellular domain of TREM-1 (rTREM-1) and an agonistic TREM-1 antibody were used to inhibit and activate TREM-1 signaling to evaluate its role in neutrophil activation, pathogen clearance, proinflammatory cytokine response, and the outcome of highly pathogenic S. suis infection in a mouse model. Blockage of TREM-1 signaling caused a more severe proinflammatory response to S. suis infection and increased the mortality rate, while its activation had the opposite effect. Blockage or activation of TREM-1 signaling lowered or raised the number of neutrophils in the blood, which correlated well with host clearance of S. suis. In conclusion, the TREM-1-mediated innate immune response played an essential role in the activation of neutrophils and S. suis clearance, which further reduced severe inflammation and finally benefited the outcome of the infection. Streptococcus suis is a major swine pathogen that is responsible for severe economic losses in the pork industry and also represents a significant threat to human health (1-3). Infection of humans could cause meningitis, sepsis, arthritis, endocarditis, and endophthalmitis, and the pooled case-fatality rate is 12.8% (4). The two large-scale human S. suis epidemics in China (the first was 25 cases with 14 deaths in Jiangsu in 1998, and the second was 204 cases with 38 deaths in Sichuan in 2005) have raised people's awareness of the public health threat (3, 5, 6). To date, more than 1,500 human infections have been reported worldwide (4). In addition, S. suis has also been identified as the third most common cause of community-acquired bacterial meningitis in Hong Kong and as the leading and second most common cause of adult meningitis in Vietnam and Thailand, respectively (3,7,8). S. suis is known to constitute a high risk of infection for occupationally exposed people (9-11), but it could also cause severe infection in people who lack contact with swine and pork-derived products (12, 13). Human S. suis isolates showed high adhesion to intestinal epithelial cells, suggesting that it should be considered a foodborne pathogen (14). Furthermore, S. suis infection is very dangerous for cancer patients (15), alcoholics (16), and splenectomy patients (17, 18). S. suis infection may also cause adverse clinical outcomes for people with influenza (19,20).A few comprehensive studies have been performed that yielded many advances in epidemiology, population genomics, serotyping, molecular diagnostics, the characterization of potential virulence factors, host-pathogen i...

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

TREM-1 Signaling Promotes Host Defense during the Early Stage of Infection with Highly Pathogenic Streptococcus suis

et al. 2015

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“…While, high levels of sTREM-1 have been found in patients with severe forms of allergic asthma (Bucova et al, 2012), it has been suggested that sTREM-1 may have an antiinflammatory role, by acting through a mechanism whereby sTREM blocks interactions of membrane-bound TREM-1 with its natural ligand in a way similar to the recognized interaction between the soluble form of the TNF-α receptor and membrane TNF-α receptor (Gibot and Massin, 2006; Science Publications -Bourboulis et al, 2008). Furthermore, it has been suggested that sTREM could be used as therapeutic for inflammatory conditions such as rheumatoid arthritis and sepsis (Kim et al, 2012;Wang et al, 2012). The cytokine array used in this study measures both membrane and soluble forms of TREM-1, therefore, further analysis of the effect of Moringa on this cytokine is needed.…”

Section: Discussionmentioning

confidence: 99%

Moringa Tea Blocks Acute Lung Inflammation Induced by Swine Confinement Dust Through a Mechanism Involving TNF-Î± Expression, C-Jun N-Terminal Kinase Activation and Neutrophil Regulation

McKnight¹

2014

American Journal of Immunology

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Plant based products represent a promising alternative to conventional treatments for inflammation. Moringa oleifera Lam is a tree rich in proteins, vitamins, minerals and a variety of phytochemcals with health benefits. Among the reported health benefits are antioxidant and anti-inflammatory properties. The purpose of this study was to investigate whether tea brewed from dried Moringa leaves would abrogate inflammation in a mouse model of acute lung inflammation induced by LPS or extracts prepared from dust collected from a swine confinement facility (DE). Mice were offered water or Moringa tea for seven days. Tea consumption was significantly greater than that of water consumption on days 1 and 6, but there were no significant differences in weight gain or food consumption. On day seven, mice from both groups were forced to inhale, via intranasal challenge, either Phosphate Buffered Saline (PBS), Lipopolysaccharide (LPS) [10 µg mLCompared to mice that drank water, mice that drank Moringa tea had significantly less protein (p<0.05) and cellular influx (p<0.0001) into the lung after inhalation of 10% DE. No difference in neutrophil migration into the lungs of water and M. tea groups after LPS or DE challenge was detected. But mice that drank tea had significantly (p<0.05) more neutrophils with apoptotic morphology after DE challenge. TNF-α expression 24 h after inhalation of 10% DE, was significantly higher (p<0.05) in lungs of M. tea mouse group as compared to water group. This increase in TNF-α was accompanied by higher levels of pro and anti-inflammatory cytokines. Finally, activation of c-Jun N-terminal Kinase (JNK) in lungs of M. tea+DE group 24 h post inhalation was decreased. Taken together these results suggest that Moringa oleifera leaf tea exerts antiinflammatory properties on acute lung inflammation induced by swine confinement dust through a mechanism involving neutrophil regulation and JNK activation.

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“…In general the outcome depends on whether TREM-1 is neutralized or the gene deleted. Neutralization of TREM-1 attenuates inflammation, preventing experimentally induced bacterial septic shock [36][37][38][39][40][41][42] and attenuating disease severity in mice infected with Leishmania major, influenza virus and Legionella pneumophila. 43 However, the situation for Klebsiella pneumoniae appears to be different with TREM-1/3-deficient mice showing impaired host defence, 44 similar to that observed for pneumococcal pneumonia 45 and Pseudomonas aeruginosa 8 in the same mice.…”

Section: Articlesmentioning

confidence: 99%

Reversal of TREM-1 ectodomain shedding and improved bacterial clearance by intranasal metalloproteinase inhibitors

et al. 2017

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Triggering receptor expressed on myeloid cells-1 (TREM-1) is expressed on neutrophils and monocyte/macrophages and amplifies Toll-like receptor-mediated inflammation during infection. TREM-1 also exists in an antagonistic soluble form (sTREM-1) that has been used as a peripheral biomarker in sepsis, though the mechanisms of its release are not entirely clear. The requirement of TREM-1 in single microbial infections is controversial, with some studies showing a protective role and others a contribution to immunopathology. Furthermore, the role of membrane-bound and sTREM-1 in polygenic infections is currently unknown. In a mouse co-infection model where preceding viral infection greatly enhances bacteria co-infection, we now determine a mechanisms for the striking increase in sTREM-1 and the loss of TREM-1 on surface of neutrophils. We identified a matrix metalloproteinase (MMP)-9 cleavage site in TREM-1 and that the increase of MMP-9 in bronchoalveolar lavage fluid mirrors sTREM-1 release. In vitro studies with neutrophils and MMP-9 and the reduction of sTREM-1 in vivo after MMP-9 inhibition verifies that this enzyme cleaves TREM-1. Intriguingly, MMP-9 inhibition significantly reduces bacterial load and ensuing immunopathology in a co-infection model. This highlights MMP-9 inhibition as a potential therapeutic via blocking cleavage of TREM-1.

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Blocking TREM-1 signaling prolongs survival of mice with Pseudomonas aeruginosa induced sepsis

Cited by 51 publications

References 27 publications

TREM-1 Signaling Promotes Host Defense during the Early Stage of Infection with Highly Pathogenic Streptococcus suis

TREM-1 Signaling Promotes Host Defense during the Early Stage of Infection with Highly Pathogenic Streptococcus suis

Moringa Tea Blocks Acute Lung Inflammation Induced by Swine Confinement Dust Through a Mechanism Involving TNF-Î± Expression, C-Jun N-Terminal Kinase Activation and Neutrophil Regulation

Reversal of TREM-1 ectodomain shedding and improved bacterial clearance by intranasal metalloproteinase inhibitors

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