Modulation of the Triggering Receptor Expressed on Myeloid Cells–1 Pathway during Pneumonia in Rats

Gibot, Sébastien; Alauzet, Corentine; Massin, Frédéric; Sennoune, Nassira; Fauré, G; Béné, Marie‐Christine; Lozniewski, Alain; Bollaert, Pierre‐Édouard; Lévy, Bruno

doi:10.1086/506950

Cited by 80 publications

(80 citation statements)

References 25 publications

(41 reference statements)

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“…Furthermore, in accordance with our findings in antibody experiments, Pilrb Ϫ/Ϫ mice were more resistant to infection than were WT mice and exhibited decreased bacterial burden and greater survival. A similar protective phenotype was observed during Pseudomonas aeruginosa induced-pneumonia in rats wherein blocking TREM-1 by using LP17 peptide appeared to be beneficial (16). In a lipopolysaccharide (LPS)-induced septic shock model, 100% mortality was observed in mice injected with an agonist TREM-1 antibody.…”

Section: Discussionsupporting

confidence: 52%

Modulation of Paired Immunoglobulin-Like Type 2 Receptor Signaling Alters the Host Response toStaphylococcus aureus-Induced Pneumonia

Banerjee¹,

Stevenaert²,

Pande³

et al. 2010

Infect Immun

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Paired immunoglobulin-like type 2 receptors (PILRs) inhibitory PILR␣ and activating PILR␤ are predominantly expressed on myeloid cells. Their functions in host defense and inflammation are largely unknown, and in this study, we evaluated their roles in an acute Staphylococcus aureus pneumonia model. Compared to their respective controls, Pilrb ؊/؊ mice or mice in which PILR␣ was activated with an agonistic antibody showed improved clearance of pulmonary staphylococci and improved survival. These mice had reduced serum or bronchoalveolar lavage fluid levels of interleukin-1␤ (IL-1␤), tumor necrosis factor alpha (TNF-␣), and IL-6 and elevated levels of gamma interferon (IFN-␥), IL-12, and IL-10. In contrast, mice in which PILR␤ was activated had increased lung bacterial burdens and higher mortality coupled with an intense proinflammatory response with highly elevated levels of IL-1␤, TNF-␣, and IL-6. Treatment groups with reduced bacterial burdens had higher levels of Keratinocyte-derived chemokine (KC), macrophage inflammatory protein 2 (MIP-2), and MIP-1␣ in bronchoalveolar lavage fluid and an increased influx of neutrophils and macrophages to the lungs. Consistent with our in vivo findings, bone marrow-derived macrophages from Pilrb ؊/؊ mice released significantly less IL-1␤ and TNF-␣ and more IFN-␥ and IL-12 than did the wild-type macrophages when directly stimulated with heat-killed S. aureus. To our knowledge, this is the first evidence that S. aureus directly interacts with PILR␤. It provides a mechanism by which manipulating the balance in favor of an inhibitory PILR signal, by activation of PILR␣ or deletion of PILR␤, helps to control acute S. aureus-mediated pneumonia and attenuate the inflammatory response. These results highlight the importance of PILRs in innate immunity and the control of inflammation.

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Section: Discussionsupporting

confidence: 52%

Modulation of Paired Immunoglobulin-Like Type 2 Receptor Signaling Alters the Host Response toStaphylococcus aureus-Induced Pneumonia

Banerjee¹,

Stevenaert²,

Pande³

et al. 2010

Infect Immun

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“…Gibot and colleagues examined the role of TREM-1 in bacterial pneumonia using a different approach (17). Their study involved instillation of a TREM-1-blocking peptide, LP-17, into the rat trachea following pneumonia challenge.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, numerous clinical examples of impaired neutrophil function are linked to increased rates of infection and death, including chronic granulomatous disease (CGD), neutropenic fever, and lymphocyte adhesion deficiency. However, animal studies indicate that effective bacterial clearance can be achieved in the setting of decreased inflammation (16,17). In the case of TREM-1, blockade of TREM-1 has been achieved by administering soluble forms of TREM-1, small molecule blocker (LP-17), or RNA silencing (10,18,19).…”

Section: Introductionmentioning

confidence: 99%

Transepithelial migration of neutrophils into the lung requires TREM-1

Klesney-Tait¹,

Keck²,

Li³

et al. 2012

J. Clin. Invest.

129

159

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Acute respiratory infections are responsible for more than 4 million deaths each year. Neutrophils play an essential role in the innate immune response to lung infection. These cells have an armamentarium of pattern recognition molecules and antimicrobial agents that identify and eliminate pathogens. In the setting of infection, neutrophil triggering receptor expressed on myeloid cells 1 (TREM-1) amplifies inflammatory signaling. Here we demonstrate for the first time that TREM-1 also plays an important role in transepithelial migration of neutrophils into the airspace. We developed a TREM-1/3-deficient mouse model of pneumonia and found that absence of TREM-1/3 markedly increased mortality following Pseudomonas aeruginosa challenge. Unexpectedly, TREM-1/3 deficiency resulted in increased local and systemic cytokine production. TREM-1/3-deficient neutrophils demonstrated intact bacterial killing, phagocytosis, and chemotaxis; however, histologic examination of TREM-1/3-deficient lungs revealed decreased neutrophil infiltration of the airways. TREM-1/3-deficient neutrophils effectively migrated across primary endothelial cell monolayers but failed to migrate across primary airway epithelia grown at the air-liquid interface. These data define a new function for TREM-1 in neutrophil migration across airway epithelial cells and suggest that it amplifies inflammation through targeted neutrophil migration into the lung.

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“…In fine, LP17 treatment improved survival. 36 In Southeast Asia and northern Australia the Gram-negative bacillus Burkholderia pseudomallei is an important cause of community-acquired sepsis. More than half of these cases of melioidosis, as this severe infection is named, habitually present with pneumonia, frequently associated with bacterial dissemination to distant sites.…”

Section: Trem-1 Structure and Functionmentioning

confidence: 99%

Triggering receptor expressed on myeloid cells -1 as a new therapeutic target during inflammatory diseases

Derive¹,

Massin

Gibot³

2010

Self/Nonself

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Modulation of the Triggering Receptor Expressed on Myeloid Cells–1 Pathway during Pneumonia in Rats

Abstract: The modulation of the TREM-1 pathway by the use of such synthetic peptides as LP17 appears beneficial during P. aeruginosa pneumonia in rats in attenuating lung and systemic inflammatory responses.

Cited by 80 publications

References 25 publications

Modulation of Paired Immunoglobulin-Like Type 2 Receptor Signaling Alters the Host Response toStaphylococcus aureus-Induced Pneumonia

Modulation of Paired Immunoglobulin-Like Type 2 Receptor Signaling Alters the Host Response toStaphylococcus aureus-Induced Pneumonia

Transepithelial migration of neutrophils into the lung requires TREM-1

Triggering receptor expressed on myeloid cells -1 as a new therapeutic target during inflammatory diseases

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