Journal Article

Virus-helminth co-infection reveals a microbiota-independent mechanism of immuno-modulation

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

2014

Overview

The mammalian intestine is colonized by beneficial commensal bacteria and is a site of infection by pathogens, including helminth parasites. Helminths induce potent immuno-modulatory 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 co-infection. Helminth co-infection 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 immuno-modulation occurs independently of changes in the microbiota but is dependent on Ym1.