title: Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation.
abstract: The mammalian intestine is colonized by beneficial commensal bacteria and is a site of infection by pathogens, including helminth parasites. Helminths induce potent immunomodulatory effects, but whether these effects are mediated by direct regulation of host immunity or indirectly through eliciting changes in the microbiota is unknown. We tested this in the context of virus-helminth coinfection. Helminth coinfection resulted in impaired antiviral immunity and was associated with changes in the microbiota and STAT6-dependent helminth-induced alternative activation of macrophages. Notably, helminth-induced impairment of antiviral immunity was evident in germ-free mice, but neutralization of Ym1, a chitinase-like molecule that is associated with alternatively activated macrophages, could partially restore antiviral immunity. These data indicate that helminth-induced immunomodulation occurs independently of changes in the microbiota but is dependent on Ym1.
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Osborne
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Monticelli
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Nice
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK.
authors.forename: Tara E
authors.initials: TE
authors.lastname: Sutherland
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Siracusa
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Medicine, Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hepworth
authors.affiliation: Department of Medicine, Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Vesselin T
authors.initials: VT
authors.lastname: Tomov
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Kobuley
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Sara V
authors.initials: SV
authors.lastname: Tran
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Bittinger
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Aubrey G
authors.initials: AG
authors.lastname: Bailey
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Alice L
authors.initials: AL
authors.lastname: Laughlin
authors.affiliation: Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Université Paris Descartes, Paris, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Boucher
authors.affiliation: Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Frederic D
authors.initials: FD
authors.lastname: Bushman
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Allen
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. dartis@mail.med.upenn.edu.
authors.forename: David
authors.initials: D
authors.lastname: Artis
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017250:Caliciviridae Infections / Q000276:immunology*; D060085:Coinfection / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D005759:Gastroenteritis / Q000276:immunology* / Q000821:virology; D005856:Germ-Free Life; D056747:Immunomodulation; D007422:Intestines / Q000276:immunology / Q000382:microbiology / Q000821:virology; D037102:Lectins / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000276:immunology*; D029322:Norovirus / Q000276:immunology*; D014234:Trichinella / Q000276:immunology*; D014235:Trichinellosis / Q000276:immunology*; D001619:beta-N-Acetylhexosaminidases / Q000276:immunology*
chemical_list: D037102:Lectins; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases
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