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

• Published in: Science (American Association for the Advancement of Science) Vol. 345; no. 6196; pp. 578 - 582
• Main Authors: Osborne, Lisa C., Monticelli, Laurel A., Nice, Timothy J., Sutherland, Tara E., Siracusa, Mark C., Hepworth, Matthew R., Tomov, Vesselin T., Kobuley, Dmytro, Tran, Sara V., Bittinger, Kyle, Bailey, Aubrey G., Laughlin, Alice L., Boucher, Jean-Luc, Wherry, E. John, Bushman, Frederic D., Allen, Judith E., Virgin, Herbert W., Artis, David
• Format: Journal Article
• Language: English
• Published: Washington American Association for the Advancement of Science 01-08-2014; The American Association for the Advancement of Science
• Subjects: Antivirals; Coinfection; Containment; Flavours; Helminthiasis; Immune systems; Immunity; Immunology; Immunomodulation; Infections; Macrophages; Mice; Microbiology; Microbiota; Parasites; Parasitology; Pathogens; Spleen; T lymphocytes; Virology; Viruses; Worms
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1256942

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.