title: Type I interferon signalling is not required for the induction of endotoxin tolerance.
abstract: Endotoxin, or LPS tolerance, is an immunomodulatory mechanism that results in a significantly diminished response to secondary LPS exposure, which may serve to protect the host against endotoxic shock. Type I interferons (IFNs) are cytokines released upon LPS binding to TLR4 and have been shown to have immunomodulatory properties. Due to this regulatory function of type I IFN, we aimed to investigate the role of type I IFN signalling in LPS tolerance. Our data suggests that type I IFN does not play a role in LPS tolerance in vitro, as both wild type and IFNAR1-/-peritoneal macrophages showed reduced cytokine production after secondary LPS exposure. Furthermore, both wild type and IFNAR1-/-mice were protected from a lethal dose of LPS after receiving three small doses to induce tolerance. However, IFNAR-/-mice seemed to recover faster than wild type mice, suggesting type I IFN signalling plays a detrimental role in LPS-induced sepsis. Although type I IFN may have a regulatory function in microbial infections, it does not seem to play a role in endotoxin tolerance. Type I IFN involvement in bacterial infection remains complex and further studies are needed to define the regulatory function of type I IFN signalling.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton L8S 4K1, Canada.
authors.forename: Yalda
authors.initials: Y
authors.lastname: Karimi
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton L8S 4K1, Canada.
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Poznanski
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton L8S 4K1, Canada.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Vahedi
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton L8S 4K1, Canada.
authors.forename: Branson
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton L8S 4K1, Canada.
authors.forename: Marianne V
authors.initials: MV
authors.lastname: Chew
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton L8S 4K1, Canada.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Lee
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton L8S 4K1, Canada. Electronic address: ashkara@mcmaster.ca.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Ashkar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004361:Drug Tolerance; D007370:Interferon Type I / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D012772:Shock, Septic / Q000276:immunology*; D015398:Signal Transduction
chemical_list: C507964:IFNAR1 protein, human; D007370:Interferon Type I; D008070:Lipopolysaccharides; D053633:Receptor, Interferon alpha-beta
keywords: LPS tolerance; Type I Interferon