title: Targeting TREM-1 Signaling in the Presence of Antibiotics is Effective Against Streptococcal Toxic-Shock-Like Syndrome (STSLS) Caused by Streptococcus suis.
abstract: Streptococcus suis (S.suis), a major swine pathogen, is also a severe threat to human health. Infection with highly virulent strains of S. suis can cause human Streptococcal toxic-shock-like syndrome (STSLS), which is associated with high serum pro-inflammatory cytokine levels and a high mortality rate. Our previous study indicated that highly virulent S. suis infection could activate the TREM-1 signaling pathway, which promotes host clearance of S. suis during early infection. However, it remained to be elicited whether TREM-1 signaling could be a target against STSLS in the presence of antibiotic. In the present study, mice were infected with a highly virulent S. suis strain and then treated with rTREM-1 (the recombinant extracellular domain of TREM-1) to block TREM-1 signaling, antibiotics, both rTREM-1 and antibiotics, or PBS. The survival rates, clinical signs, serum IL-1β and TNF-α levels, and serum bacterial loads were evaluated. Treatment with rTREM-1 could aggravate the outcome of infection as described previously. Although the conventional treatment with antibiotics contributed to effective S. suis clearance, it did not improve survival significantly. In comparison, due to the reduction of the exaggerated pro-inflammatory response, treatment combined with rTREM-1 and antibiotics not only led to efficient bacterial clearance but also alleviated inflammation. In conclusion, TREM-1 signaling contributed to severe inflammatory response and benefited S. suis clearance. Therefore, blocking TREM-1 signaling could still be a target for the treatment of STSLS in the presence of antibiotics.
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University Wuhan, China ; College of Veterinary Medicine, Huazhong Agricultural University Wuhan, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University Wuhan, China ; College of Veterinary Medicine, Huazhong Agricultural University Wuhan, China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University Wuhan, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Lin
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University Wuhan, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Pan
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fu
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University Wuhan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University Wuhan, China ; College of Veterinary Medicine, Huazhong Agricultural University Wuhan, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Jin
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University Wuhan, China ; College of Veterinary Medicine, Huazhong Agricultural University Wuhan, China ; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University Wuhan, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University Wuhan, China ; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Huazhong Agricultural University Wuhan, China.
authors.forename: Anding
authors.initials: A
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D058491:Bacterial Load; D001769:Blood / Q000276:immunology / Q000382:microbiology; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D007155:Immunologic Factors / Q000008:administration & dosage*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D011971:Receptors, Immunologic / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012772:Shock, Septic / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000473:pathology; D017011:Streptococcus suis / Q000187:drug effects / Q000502:physiology; D016019:Survival Analysis; D016896:Treatment Outcome; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
keywords: Streptococcal toxic-shock-like syndrome (STSLS); Streptococcus suis (S. suis); Triggering receptor expressed on myeloid cells-1 (TREM-1); anti-inflammatory treatment; treatments targets