Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response

• Type of Material: Article
• Authors: Tiffany A. Reese, University of Texas Southwestern Medical Center; Kevin Bi, Dana-Farber Cancer Institute; Amal Kambal, Washington University; Ali Filali-Mouhim, Case Western Reserve University; Lalit K. Beura, University of Minnesota; Matheus C. Burger, University of São Paulo; Bali Pulendran, Emory University; Rafick Sekaly, Case Western Reserve University; Stephen C Jameson, University of Minnesota; David Masopust, University of Minnesota; W. Nicholas Haining, Dana-Farber Cancer Institute; Herbert W. Virgin, Washington University
• Language: English
• Date: 2016-05-11
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.chom.2016.04.003
• Title of Journal or Parent Work: Cell Host and Microbe
• ISSN: 1931-3128
• Volume: 19
• Issue: 5
• Start Page: 713
• End Page: 719
• Grant/Funding Information: NIH awards R24 OD019793, R01 OD011170, R01 AI111918, and R01 DK101354 supported HWV. Damon Runyon Postdoctoral Fellowship supported TAR; A core funded by NIH P30AR048335 provided experimental support
• Keywords: MICE; INFLAMMATION; Parasitology; Virology; HUMORAL RESPONSES; SUPPRESSION; SYSTEM; Science & Technology; HERPESVIRUS; Life Sciences & Biomedicine; Microbiology; 17D VACCINE; BACTERIAL-INFECTION; DISEASE; YELLOW-FEVER VACCINE
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

Abstract

Summary Immune responses differ between laboratory mice and humans. Chronic infection with viruses and parasites are common in humans, but are absent in laboratory mice, and thus represent potential contributors to inter-species differences in immunity. To test this, we sequentially infected laboratory mice with herpesviruses, influenza, and an intestinal helminth and compared their blood immune signatures to mock-infected mice before and after vaccination against yellow fever virus (YFV-17D). Sequential infection altered pre- and post-vaccination gene expression, cytokines, and antibodies in blood. Sequential pathogen exposure induced gene signatures that recapitulated those seen in blood from pet store-raised versus laboratory mice, and adult versus cord blood in humans. Therefore, basal and vaccine-induced murine immune responses are altered by infection with agents common outside of barrier facilities. This raises the possibility that we can improve mouse models of vaccination and immunity by selective microbial exposure of laboratory animals to mimic that of humans.