Microbial Exposure Enhances Immunity to Pathogens Recognized by TLR2 but Increases Susceptibility to Cytokine Storm through TLR4 Sensitization
Matthew A. Huggins,
Frances V. Sjaastad,
Mark Pierson,
Tamara A. Kucaba,
Whitney Swanson,
Christopher Staley,
Alexa R. Weingarden,
Isaac J. Jensen,
Derek B. Danahy,
Vladimir P. Badovinac,
Stephen C. Jameson,
Vaiva Vezys,
David Masopust,
Alexander Khoruts,
Thomas S. Griffith,
Sara E. Hamilton
Affiliations
Matthew A. Huggins
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
Frances V. Sjaastad
Microbiology, Immunology, and Cancer Biology PhD Program, University of Minnesota, Minneapolis, MN, USA
Mark Pierson
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
Tamara A. Kucaba
Department of Urology, University of Minnesota, Minneapolis, MN, USA
Whitney Swanson
Department of Urology, University of Minnesota, Minneapolis, MN, USA
Christopher Staley
Department of Surgery, University of Minnesota, Minneapolis, MN, USA
Alexa R. Weingarden
Department of Soil, Water, and Climate and The BioTechnology Institute, University of Minnesota, St. Paul, MN, USA
Isaac J. Jensen
Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USA
Derek B. Danahy
Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USA
Vladimir P. Badovinac
Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USA; Department of Pathology, University of Iowa, Iowa City, IA, USA; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA
Stephen C. Jameson
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA; Microbiology, Immunology, and Cancer Biology PhD Program, University of Minnesota, Minneapolis, MN, USA; Center for Immunology, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA
Vaiva Vezys
Microbiology, Immunology, and Cancer Biology PhD Program, University of Minnesota, Minneapolis, MN, USA; Center for Immunology, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA
David Masopust
Microbiology, Immunology, and Cancer Biology PhD Program, University of Minnesota, Minneapolis, MN, USA; Center for Immunology, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA
Alexander Khoruts
Microbiology, Immunology, and Cancer Biology PhD Program, University of Minnesota, Minneapolis, MN, USA; Center for Immunology, University of Minnesota, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA
Thomas S. Griffith
Microbiology, Immunology, and Cancer Biology PhD Program, University of Minnesota, Minneapolis, MN, USA; Department of Urology, University of Minnesota, Minneapolis, MN, USA; Center for Immunology, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Minneapolis VA Health Care System, Minneapolis, MN, USA; Corresponding author
Sara E. Hamilton
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA; Microbiology, Immunology, and Cancer Biology PhD Program, University of Minnesota, Minneapolis, MN, USA; Center for Immunology, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Corresponding author
Summary: Microbial exposures can define an individual’s basal immune state. Cohousing specific pathogen-free (SPF) mice with pet store mice, which harbor numerous infectious microbes, results in global changes to the immune system, including increased circulating phagocytes and elevated inflammatory cytokines. How these differences in the basal immune state influence the acute response to systemic infection is unclear. Cohoused mice exhibit enhanced protection from virulent Listeria monocytogenes (LM) infection, but increased morbidity and mortality to polymicrobial sepsis. Cohoused mice have more TLR2+ and TLR4+ phagocytes, enhancing recognition of microbes through pattern-recognition receptors. However, the response to a TLR2 ligand is muted in cohoused mice, whereas the response to a TLR4 ligand is greatly amplified, suggesting a basis for the distinct response to Listeria monocytogenes and sepsis. Our data illustrate how microbial exposure can enhance the immune response to unrelated challenges but also increase the risk of immunopathology from a severe cytokine storm. : Cohousing of laboratory mice with pet store animals changes the immune system and alters responsiveness to future challenges. Huggins et al. demonstrate that microbial exposure results in alterations to immune cells, serum cytokines, and microbiome composition. This study shows that cohousing alters the ability to detect pathogens through pattern-recognition receptors. Keywords: infection, Listeria monocytogenes, polymicrobial sepsis, Toll-like receptors, physiological microbial exposure, microbiome
