Microbial Exposure Enhances Immunity to Pathogens Recognized by TLR2 but Increases Susceptibility to Cytokine Storm through TLR4 Sensitization | Zendy

Matthew A. Huggins | Zendy; Frances V. Sjaastad | Zendy; Mark Pierson | Zendy; Tamara A. Kucaba | Zendy; Whitney Swanson | Zendy; Christopher Staley | Zendy; Alexa R. Weingarden | Zendy; Isaac J. Jensen | Zendy; Derek B. Danahy | Zendy; Vladimir P. Badovinac | Zendy; Stephen C. Jameson | Zendy; Vaiva Vezys | Zendy; David Masopust | Zendy; Alexander Khoruts | Zendy; Thomas S. Griffith | Zendy; Sara E. Hamilton | Zendy

Open Access

Microbial Exposure Enhances Immunity to Pathogens Recognized by TLR2 but Increases Susceptibility to Cytokine Storm through TLR4 Sensitization

Author(s) -

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

Publication year - 2019

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2019.07.028

Subject(s) - immunology , tlr2 , immune system , cytokine storm , biology , listeria monocytogenes , tlr4 , innate immune system , cytokine , microbiology and biotechnology , toll like receptor , immunity , sepsis , pathogen , pattern recognition receptor , acquired immune system , inflammation , sensitization , medicine , bacteria , infectious disease (medical specialty) , disease , genetics , covid-19

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.

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