title: Prognostic value and therapeutic potential of TREM-1 in Streptococcus pyogenes- induced sepsis.
abstract: TREM-1 (triggering receptor expressed on myeloid cells) is a surface molecule expressed on neutrophils and macrophages which has been implicated in the amplification of inflammatory responses triggered during infection. In the present study, we have investigated the clinical significance of TREM-1 in Streptococcus pyogenes-induced severe sepsis in both experimentally infected mice as well as in patients with streptococcal toxic shock. We found that S. pyogenes induced a dose-dependent upregulation of TREM-1 in in vitro cultured phagocytic cells and in the organs of S. pyogenes-infected mice. Furthermore, we reported a positive correlation between serum levels of soluble TREM-1 (sTREM-1) and disease severity in infected patients as well as in experimentally infected mice. Hence, sTREM-1 may represent a useful surrogate marker for streptococcal sepsis. We found that modulation of TREM-1 by administration of the TREM-1 decoy receptor rTREM-1/Fc substantially attenuated the synthesis of inflammatory cytokines. More importantly, treatment of S. pyogenes-infected septic mice with rTREM-1/Fc or the synthetically produced conserved extracellular domain LP17 significantly improved disease outcome. In summary, our data suggest that TREM-1 may not only represent a valuable marker for S. pyogenes infection severity but it may also be an attractive target for the treatment of streptococcal sepsis.
authors.affiliation: Infection Immunology Research Group, Department of Microbial Pathogenesis, Helmholtz Center for Infection Research, Braunschweig, Germany.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Horst
authors.forename: Anna
authors.initials: A
authors.lastname: Linnér
authors.forename: Andreas
authors.initials: A
authors.lastname: Beineke
authors.forename: Sabine
authors.initials: S
authors.lastname: Lehne
authors.forename: Claudia
authors.initials: C
authors.lastname: Höltje
authors.forename: Alexander
authors.initials: A
authors.lastname: Hecht
authors.forename: Anna
authors.initials: A
authors.lastname: Norrby-Teglund
authors.forename: Eva
authors.initials: E
authors.lastname: Medina
authors.forename: Oliver
authors.initials: O
authors.lastname: Goldmann
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008856:Microscopy, Fluorescence; D011379:Prognosis; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D012772:Shock, Septic / Q000097:blood / Q000276:immunology / Q000382:microbiology; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D016019:Survival Analysis; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007141:Immunoglobulin Fc Fragments; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C408842:TREM1 protein, human; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha