A helminth secretory product enhances enteric adenovirus infection independent of tuft cells and type 2 immunity 2493

Abstract Description Parasitic worms (helminths) infect nearly 25% of the global population, often establishing long-term residence in the GI tract. Helminths share a striking geographic co-occurrence with certain microbial infections, and clinical data suggest that helminth-colonized people suffer worse outcomes to such infections. In mice, helminths promote norovirus and West Nile virus infection through tuft cell- and IL-4Ra/STAT6-driven type 2 inflammation, which dampens antiviral immunity. To specifically probe helminth-virus interactions at the small intestine (SI) epithelium, we established a co-infection model of H. polygyrus (“Hp”) (parasitic roundworm, long-term residence in SI lumen) and mouse adenovirus 2 (“MAdV2”) (infects SI epithelial cells). Mice infected with MAdV2 alone rapidly cleared the virus, whereas Hp/MAdV2-coinfected animals had 103-105-fold higher titers that persisted for weeks. Interestingly, MAdV2 enhancement by Hp did not require tuft cells or any tested component of type 2 immunity (IL-4Ra, IL-5, IL-25, ST2). Furthermore, viral enhancement was not due to impaired antiviral immunity, as Hp enhanced MAdV2 similarly in WT, Rag2; Il2rg-DKO, and Stat1-KO mice. Instead, helminth-conditioned media promoted MAdV2 infection of epithelial cells in vitro and in vivo. These data prompt the hypothesis that a helminth-secreted product promotes MAdV2 infection independent of tuft cells and type 2 immunity. Funding Sources Supported by NIH/NIAID R21AI182722 (JvM) and a postdoctoral fellowship from the Institute for Translational Immunology, University of Washington (TT). Topic Categories Mucosal and Regional Immunology (MUC)