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

TitleCoinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation.
Publication TypeJournal Article
Year of Publication2014
AuthorsOsborne LC, Monticelli LA, Nice TJ, Sutherland TE, Siracusa MC, Hepworth MR, Tomov VT, Kobuley D, Tran SV, Bittinger K, Bailey AG, Laughlin AL, Boucher J-L, E Wherry J, Bushman FD, Allen JE, Virgin HW, Artis D
JournalScience
Volume345
Issue6196
Pagination578-82
Date Published2014 Aug 1
ISSN1095-9203
KeywordsAnimals, beta-N-Acetylhexosaminidases, Caliciviridae Infections, CD8-Positive T-Lymphocytes, Coinfection, Gastroenteritis, Germ-Free Life, Immunomodulation, Intestines, Lectins, Macrophage Activation, Macrophages, Mice, Mice, Inbred C57BL, Microbiota, Norovirus, Trichinella, Trichinellosis
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.

DOI10.1126/science.1256942
Alternate JournalScience
PubMed ID25082704
Grant List2-P30 CA016520 / CA / NCI NIH HHS / United States
5T32A100716334 / / PHS HHS / United States
AI061570 / AI / NIAID NIH HHS / United States
AI074878 / AI / NIAID NIH HHS / United States
AI082630 / AI / NIAID NIH HHS / United States
AI083022 / AI / NIAID NIH HHS / United States
AI087990 / AI / NIAID NIH HHS / United States
AI095466 / AI / NIAID NIH HHS / United States
AI095608 / AI / NIAID NIH HHS / United States
AI097333 / AI / NIAID NIH HHS / United States
AI102942 / AI / NIAID NIH HHS / United States
AI106697 / AI / NIAID NIH HHS / United States
F32-AI085828 / AI / NIAID NIH HHS / United States
HHSN272201300006C / / PHS HHS / United States
K08-DK097301 / DK / NIDDK NIH HHS / United States
MR/J001929/1 / / Medical Research Council / United Kingdom
P30-AI045008 / AI / NIAID NIH HHS / United States
P30-DK050306 / DK / NIDDK NIH HHS / United States
R01 AI 084887 / AI / NIAID NIH HHS / United States
T32-AI007532 / AI / NIAID NIH HHS / United States

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