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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
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.
Abstract:
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.
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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