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Cell Host Microbe. 2016 May 11;19(5):713-9. doi: 10.1016/j.chom.2016.04.003. Epub 2016 Apr 20.

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

Author information

1
Departments of Immunology and Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: tiffany.reese@utsouthwestern.edu.
2
Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Pediatric Hematology and Oncology, Children's Hospital, Boston, MA 02115, and the Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
3
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
5
Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
6
Department of Clinical Analyses and Toxicology, School of Pharmaceutical Science at University of São Paulo, São Paulo 05508, Brazil.
7
Emory Vaccine Center, Yerkes National Primate Research Center and Department of Pathology, Emory University, Atlanta, GA 30329, USA.
8
Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
9
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: virgin@wustl.edu.

Abstract

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.

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PMID:
27107939
PMCID:
PMC4896745
DOI:
10.1016/j.chom.2016.04.003
[Indexed for MEDLINE]
Free PMC Article

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