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

Matthew A Huggins1, Frances V Sjaastad2, Mark Pierson1

  • 1Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.

Cell Reports
|August 15, 2019
PubMed

Insights

Microbial exposures alter immune cell populations and cytokine levels. This altered immune state enhances protection against Listeria monocytogenes but increases susceptibility to sepsis, highlighting a dual impact of microbiome on host defense.

Area of Science:

  • Immunology
  • Microbiology
  • Infectious Disease

Background:

  • Microbial exposures shape an individual's basal immune status.
  • Cohousing specific pathogen-free (SPF) mice with pet store mice induces systemic immune alterations, including increased phagocytes and inflammatory cytokines.

Purpose of the Study:

  • To investigate how altered basal immune states from microbial exposure influence the acute response to systemic infections.
  • To determine the differential impact of microbial exposure on responses to Listeria monocytogenes and polymicrobial sepsis.

Main Methods:

  • Cohousing SPF mice with pet store mice to establish distinct microbial exposures.
  • Challenging cohoused and control mice with virulent Listeria monocytogenes (LM) and polymicrobial sepsis models.
  • Analyzing immune cell populations (TLR2+, TLR4+ phagocytes) and cytokine profiles.

Main Results:

  • Cohoused mice showed enhanced protection against LM infection but increased morbidity and mortality in sepsis.
  • Increased Toll-like receptor 2 (TLR2) and TLR4 expressing phagocytes were observed in cohoused mice.
  • A muted response to TLR2 ligand and an amplified response to TLR4 ligand were noted in cohoused mice.

Conclusions:

  • Microbial exposure can prime the immune system for enhanced responses to certain pathogens like LM.
  • Altered immune states due to microbial exposure can increase susceptibility to severe infections like sepsis, leading to immunopathology.
  • Differential TLR responses mediate distinct outcomes in response to varied microbial challenges.

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