Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response.
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.
Departments of Immunology and Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: tiffany.reese@utsouthwestern.edu.
Tiffany A
TA
Reese
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.
Kevin
K
Bi
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Amal
A
Kambal
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Ali
A
Filali-Mouhim
Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
Lalit K
LK
Beura
Department of Clinical Analyses and Toxicology, School of Pharmaceutical Science at University of São Paulo, São Paulo 05508, Brazil.
Matheus C
MC
Bürger
Emory Vaccine Center, Yerkes National Primate Research Center and Department of Pathology, Emory University, Atlanta, GA 30329, USA.
Bali
B
Pulendran
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Rafick-Pierre
RP
Sekaly
Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
Stephen C
SC
Jameson
Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
David
D
Masopust
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.
W Nicholas
WN
Haining
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: virgin@wustl.edu.
Herbert W
HW
Virgin
D000818:Animals; D000906:Antibodies / Q000097:blood; D000914:Antibodies, Viral / Q000276:immunology; D060085:Coinfection / Q000276:immunology / Q000469:parasitology / Q000821:virology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000276:immunology; D015870:Gene Expression; D006373:Helminthiasis / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D006564:Herpesviridae / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000097:blood; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D007411:Intestinal Diseases, Parasitic / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D015004:Yellow Fever / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control* / Q000821:virology; D022341:Yellow Fever Vaccine / Q000276:immunology* / Q000494:pharmacology; D015005:Yellow fever virus / Q000276:immunology*
D000906:Antibodies; D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D022341:Yellow Fever Vaccine