Prognostic Value and Therapeutic Potential of TREM-1 in Streptococcus pyogenes-Induced Sepsis

Autor: Eva Medina, Anna Norrby-Teglund, Alexander Hecht, Andreas Beineke, Sabine Lehne, Anna Linnér, Sarah A. Horst, Oliver Goldmann, Claudia Höltje
Rok vydání: 2013
Předmět:
Zdroj: Journal of Innate Immunity. 5:581-590
ISSN: 1662-8128
1662-811X
Popis: 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.
Databáze: OpenAIRE
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