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

Tiffany A. Reese, Kevin Bi, Amal Kambal, Ali Filali-Mouhim, Lalit K. Beura, Matheus C. Bürger, Bali Pulendran, Rafick Pierre Sekaly, Stephen C. Jameson, David Masopust, W. Nicholas Haining, Herbert W. Virgin

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)713-719
Number of pages7
JournalCell Host and Microbe
Volume19
Issue number5
DOIs
StatePublished - May 11 2016

Bibliographical note

Funding Information:
We acknowledge Darren Kreamalmeyer for mouse colony management; E. Pearce and S. Huang for H. polygyrus parasites; B. Parikh and W. Yokoyama for MCMV; J. Brien and M. Diamond for YFV-17D; and the Genome Technology Access Center at Washington University for microarrays. A core funded by NIH P30AR048335 provided experimental support. NIH awards R24 OD019793, R01 OD011170, R01 AI111918, and R01 DK101354 supported H.W.V. Damon Runyon Postdoctoral Fellowship supported T.A.R.

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