title: Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors.
abstract: The genome of vertebrates contains endogenous retroviruses (ERVs) that are largely nonfunctional relicts of ancestral germline infection by exogenous retroviruses. However, in some mouse strains ERVs are actively involved in disease. Here we report that nucleic acid-recognizing Toll-like receptors 3, 7, and 9 (TLR 3, TLR7, and TLR9) are essential for the control of ERVs. Loss of TLR7 function caused spontaneous retroviral viremia that coincided with the absence of ERV-specific antibodies. Importantly, additional TLR3 and TLR9 deficiency led to acute T cell lymphoblastic leukemia, underscoring a prominent role for TLR3 and TLR9 in surveillance of ERV-induced tumors. Experimental ERV infection induced a TLR3-, TLR7-, and TLR9-dependent group of "acute-phase" genes previously described in HIV and SIV infections. Our study suggests that in addition to their role in innate immunity against exogenous pathogens, nucleic acid-recognizing TLRs contribute to the immune control of activated ERVs and ERV-induced tumors.
authors.affiliation: Institut für Immunologie, Philipps-Universität Marburg, Marburg, Germany. philipp.yu@staff.uni-marburg.de
authors.forename: Philipp
authors.initials: P
authors.lastname: Yu
authors.forename: Wolger
authors.initials: W
authors.lastname: Lübben
authors.forename: Heike
authors.initials: H
authors.lastname: Slomka
authors.forename: Janine
authors.initials: J
authors.lastname: Gebler
authors.forename: Madlen
authors.initials: M
authors.lastname: Konert
authors.forename: Chengcong
authors.initials: C
authors.lastname: Cai
authors.forename: Luisa
authors.initials: L
authors.lastname: Neubrandt
authors.forename: Olivia
authors.initials: O
authors.lastname: Prazeres da Costa
authors.forename: Stephanie
authors.initials: S
authors.lastname: Paul
authors.forename: Sonja
authors.initials: S
authors.lastname: Dehnert
authors.forename: Karolin
authors.initials: K
authors.lastname: Döhne
authors.forename: Michael
authors.initials: M
authors.lastname: Thanisch
authors.forename: Silke
authors.initials: S
authors.lastname: Storsberg
authors.forename: Lisa
authors.initials: L
authors.lastname: Wiegand
authors.forename: Andreas
authors.initials: A
authors.lastname: Kaufmann
authors.forename: Marianne
authors.initials: M
authors.lastname: Nain
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bettio
authors.forename: Barbara
authors.initials: B
authors.lastname: Schnierle
authors.forename: Larissa
authors.initials: L
authors.lastname: Kolesnikova
authors.forename: Stephan
authors.initials: S
authors.lastname: Becker
authors.forename: Markus
authors.initials: M
authors.lastname: Schnare
authors.forename: Stefan
authors.initials: S
authors.lastname: Bauer
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009696:Nucleic Acids / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D009857:Oncogenes / Q000235:genetics / Q000276:immunology; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D014766:Viremia / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D009696:Nucleic Acids; D051193:Toll-Like Receptors