Coinfection. 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

doi:10.1126/science.1256942

Coinfection. 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 journal › Article › peer-review

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.

Original language	English
Pages (from-to)	578-582
Journal	Science (New York, N.Y.)
Volume	345
Issue number	6196
DOIs	https://doi.org/10.1126/science.1256942
Publication status	Published - 1 Aug 2014

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Osborne, L. C., Monticelli, L. A., Nice, T. J., Sutherland, T., Siracusa, M. C., Hepworth, M. R., Tomov, V. T., Kobuley, D., Tran, S. V., Bittinger, K., Bailey, A. G., Laughlin, A. L., Boucher, J-L., Wherry, E. J., Bushman, F. D., Allen, J., Virgin, H. W., & Artis, D. (2014). Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation. Science (New York, N.Y.), 345(6196), 578-582. https://doi.org/10.1126/science.1256942

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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.",

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

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Osborne, LC, Monticelli, LA, Nice, TJ, Sutherland, T, Siracusa, MC, Hepworth, MR, Tomov, VT, Kobuley, D, Tran, SV, Bittinger, K, Bailey, AG, Laughlin, AL, Boucher, J-L, Wherry, EJ, Bushman, FD, Allen, J, Virgin, HW & Artis, D 2014, 'Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation.', Science (New York, N.Y.), vol. 345, no. 6196, pp. 578-582. https://doi.org/10.1126/science.1256942

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T1 - Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation.

AU - Osborne, Lisa C

AU - Monticelli, Laurel A

AU - Nice, Timothy J

AU - Sutherland, Tara

AU - Siracusa, Mark C

AU - Hepworth, Matthew R

AU - Tomov, Vesselin T

AU - Kobuley, Dmytro

AU - Tran, Sara V

AU - Bittinger, Kyle

AU - Bailey, Aubrey G

AU - Laughlin, Alice L

AU - Boucher, Jean-Luc

AU - Wherry, E John

AU - Bushman, Frederic D

AU - Allen, Judith

AU - Virgin, Herbert W

AU - Artis, David

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N2 - 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.

AB - 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.

U2 - 10.1126/science.1256942

DO - 10.1126/science.1256942

M3 - Article

C2 - 25082704

VL - 345

SP - 578

EP - 582

JO - Science

JF - Science

SN - 0036-8075

IS - 6196

ER -

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

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