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

doi:10.1016/j.chom.2016.04.003

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

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

Authors

Affiliations

¹ Departments of Immunology and Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: [email protected].
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: [email protected].

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.

MeSH terms

Animals
Antibodies / blood
Antibodies, Viral / immunology
Coinfection / immunology
Coinfection / parasitology
Coinfection / virology
Cytokines / blood
Disease Models, Animal
Fetal Blood / immunology
Gene Expression
Helminthiasis / immunology*
Helminthiasis / prevention & control
Helminthiasis / virology
Herpesviridae / immunology*
Herpesviridae Infections / immunology*
Herpesviridae Infections / prevention & control
Humans
Immunity, Innate
Immunoglobulin G / blood
Influenza, Human / immunology
Influenza, Human / prevention & control
Intestinal Diseases, Parasitic / immunology*
Intestinal Diseases, Parasitic / prevention & control
Intestinal Diseases, Parasitic / virology
Mice
Mice, Inbred C57BL
Orthomyxoviridae Infections / immunology
Orthomyxoviridae Infections / parasitology
Orthomyxoviridae Infections / prevention & control
Yellow Fever / immunology*
Yellow Fever / parasitology
Yellow Fever / prevention & control*
Yellow Fever / virology
Yellow Fever Vaccine / immunology*
Yellow Fever Vaccine / pharmacology
Yellow fever virus / immunology*

Substances

Antibodies
Antibodies, Viral
Cytokines
Immunoglobulin G
Yellow Fever Vaccine

Supplementary concepts

Intestinal helminthiasis

Abstract

MeSH terms

Substances

Supplementary concepts

Grants and funding