Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation

Lisa C Osborne, Laurel A Monticelli, Timothy J Nice, Tara Sutherland, Mark C Siracusa, Matthew R Hepworth, Vesselin T Tomov, Dmytro Kobuley, Sara V Tran, Kyle Bittinger, Aubrey G Bailey, Alice L Laughlin, Jean-Luc Boucher, E John Wherry, Frederic D Bushman, Judith Allen, Herbert W Virgin, David Artis

Research output: Contribution to journalArticlepeer-review

209 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)578-582
Number of pages5
Issue number6196
Publication statusPublished - 17 Jul 2014

Bibliographical note

095831, Wellcome Trust, United Kingdom2-P30 CA016520, NCI NIH HHS, United States5T32A100716334, PHS HHS, United StatesAI061570, NIAID NIH HHS, United StatesAI074878, NIAID NIH HHS, United StatesAI082630, NIAID NIH HHS, United StatesAI083022, NIAID NIH HHS, United StatesAI087990, NIAID NIH HHS, United StatesAI095466, NIAID NIH HHS, United StatesAI095608, NIAID NIH HHS, United StatesAI097333, NIAID NIH HHS, United StatesAI102942, NIAID NIH HHS, United StatesAI106697, NIAID NIH HHS, United StatesF32 AI085828, NIAID NIH HHS, United StatesF32-AI085828, NIAID NIH HHS, United StatesHHSN272201300006C, PHS HHS, United StatesK08 DK097301, NIDDK NIH HHS, United StatesK08-DK097301, NIDDK NIH HHS, United StatesMR/J001929/1, Medical Research Council, United KingdomP01 AI106697, NIAID NIH HHS, United StatesP30-AI045008, NIAID NIH HHS, United StatesP30-DK050306, NIDDK NIH HHS, United StatesR01 AI 084887, NIAID NIH HHS, United StatesR01 AI061570, NIAID NIH HHS, United StatesR01 AI074878, NIAID NIH HHS, United StatesR01 AI095466, NIAID NIH HHS, United StatesR01 AI097333, NIAID NIH HHS, United StatesR01 AI102942, NIAID NIH HHS, United StatesR21 AI087990, NIAID NIH HHS, United StatesT32-AI007532, NIAID NIH HHS, United StatesU01 AI095608, NIAID NIH HHS, United States


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