TREM-1 Promotes Survival during Klebsiella pneumoniae Liver Abscess in Mice

Lin, Yi Tsung; Tseng, Kai Yu; Yeh, Yi Chen; Yang, Fu Chen; Fung, Chang Phone; Chen, Nien Jung

doi:10.1128/iai.01347-13

Cited by 31 publications

(29 citation statements)

References 48 publications

(66 reference statements)

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“…However, blockage of signaling did not reduce the inflammatory response as anticipated but rather increased the level of proinflammatory cytokines. Similar results were also found for K. pneumoniae infections, in which TREM-1 signaling played an essential role in bacterial clearance (37). Therefore, we investigated the effect of TREM-1 signaling on bacterial clearance as described previously (37)(38)(39)45).…”

Section: Resultssupporting

confidence: 53%

“…For pneumococcal infection, TREM-1 did not influence neutrophil activation or phagocytosis but played a role in the responsiveness of macrophages to the infection (38). For K. pneumoniae clearance, TREM-1 played only a minor role in neutrophil recruitment and contributed to the bactericidal effect via neutrophil extracellular traps (37). A previous study indicated that neutrophils play an essential role in the control of S. suis infection (46,47), and TREM-1 signaling could significantly affect the level of MPO and the number of neutrophils in the blood in response to S. suis infection (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The effect of TREM-1 signaling on microbial control has been controversial; it could not affect the clearance of L. major, influenza virus, or L. pneumophila infection (36), but it benefitted the clearance of K. pneumoniae (37), S. pneumoniae (38,39), and P. aeruginosa (40). Furthermore, TREM-1 may clear pathogens via different mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…In the absence of TREM-1, mice exhibited reduced neutrophilic infiltration, diminished expression of proinflammatory cytokines, and attenuated disease severity without affecting pathogen clearance during Leishmania major, influenza virus, or Legionella pneumophila infection (36). In contrast, TREM-1 deficiency increased Klebsiella pneumoniae dissemination, enhanced liver and systematic inflammation, and reduced survival in a K. pneumoniae liver abscess model (37). TREM-1/3 deficiency also led to increased lethality accompanied by enhanced Streptococcus pneumoniae growth at the primary site of infection, increased dissemination, reduced local release of cytokines and chemokines, and a delayed influx of neutrophils (38).…”

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confidence: 96%

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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: Resultssupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

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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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“…That instinct was verifiedby another lab, who determined that TREM-1 knockout mice showed a much lower survival rate than wild type controls (28.6% vs. 61.9%, respectively) when exposed to Klebsiellapneumonia infection. The impaired survival was due to an increase in liver damage paired with diminished bacterial clearance in the TREM-1 −/− mice [39]. This notion was again confirmed in a study where TREM-1 expression in the presence of Pneumococcal pneumonia infection led to an improved bacterial clearance and improved survival [40].…”

Section: Triggering Receptor Expressed On Myeloid Cells-1mentioning

confidence: 79%

Single versus combined immunoregulatory approach using PD-1 and CTLA-4 modulators in controlling sepsis

Rudick

Cornell

Agrawal

2017

Expert Review of Clinical Immunology

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Introduction: Sepsis is a disease process characterized by an extreme inflammatory response followed by a period of severe immunosuppression. In recent years, there has been improved survival in the initialimmune response during systemic inflammatory response syndrome, and compensatory anti-inflammatory response, yet is mostly unchanged with 18–30% mortality during the laterstage of sepsis despite numerous Phase 3 clinical trials. Areas covered: This review article presents a critical evaluation of the most promising newer studies aimed at improving the immunosuppressive stage of sepsis. Administration of DHEA/AED/AET show promise in improving survival. Blockade of signaling pathways for PD-1/PD-L1/CTLA-4, and partial blockade of TREM-1 signaling, and modification to sTREM-1 and the JAK/STAT pathway are promising methods of restoring host immune response and improving survival. While there has been significant progress, currently no findings have been translated into effective clinical interventions. Expert Commentary: Clinical success by immunomodulation with individual immune mediator is encouraging and should progress to evaluating combined methods of immunoregulation. Since most of the animal studies do not reproduce human sepsis, development of better animal models and moving toward human studies for intervention will lead to the most beneficial findings in translational science.

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