Title | Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Osborne, 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 |
Journal | Science |
Volume | 345 |
Issue | 6196 |
Pagination | 578-82 |
Date Published | 2014 Aug 1 |
ISSN | 1095-9203 |
Keywords | Animals, 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 | <p>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.</p> |
DOI | 10.1126/science.1256942 |
Alternate Journal | Science |
PubMed ID | 25082704 |
PubMed Central ID | PMC4548887 |
Grant List | 095831 / / Wellcome Trust / United Kingdom 2-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 F32-AI085828 / AI / NIAID NIH HHS / United States HHSN272201300006C / / PHS HHS / United States K08 DK097301 / DK / NIDDK NIH HHS / United States K08-DK097301 / DK / NIDDK NIH HHS / United States MR/J001929/1 / / Medical Research Council / United Kingdom P01 AI106697 / AI / NIAID NIH HHS / United States 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 R01 AI061570 / AI / NIAID NIH HHS / United States R01 AI074878 / AI / NIAID NIH HHS / United States R01 AI095466 / AI / NIAID NIH HHS / United States R01 AI097333 / AI / NIAID NIH HHS / United States R01 AI102942 / AI / NIAID NIH HHS / United States R21 AI087990 / AI / NIAID NIH HHS / United States T32-AI007532 / AI / NIAID NIH HHS / United States U01 AI095608 / AI / NIAID NIH HHS / United States |