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.
1.Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA 2.Univ Minnesota, Microbiol Immunol & Canc Biol PhD Program, Minneapolis, MN 55455 USA 3.Univ Minnesota, Dept Urol, Minneapolis, MN 55455 USA 4.Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA 5.Univ Minnesota, Dept Soil Water & Climate, St Paul, MN 55108 USA 6.Univ Minnesota, BioTechnol Inst, St Paul, MN 55108 USA 7.Univ Iowa, Interdisciplinary Grad Program Immunol, Iowa City, IA USA 8.Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA 9.Univ Iowa, Dept Microbiol & Immunol, Iowa City, IA USA 10.Univ Minnesota, Ctr Immunol, Minneapolis, MN 55455 USA 11.Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA 12.Univ Minnesota, Dept Microbiol & Immunol, Minneapolis, MN USA 13.Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA 14.Minneapolis VA Hlth Care Syst, Minneapolis, MN 55417 USA
Recommended Citation:
Huggins, Matthew A.,Sjaastad, Frances V.,Pierson, Mark,et al. Microbial Exposure Enhances Immunity to Pathogens Recognized by TLR2 but Increases Susceptibility to Cytokine Storm through TLR4 Sensitization[J]. CELL REPORTS,2019-01-01,28(7):1729-+