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Published on: February 22, 2017
Low-Dose Lipopolysaccharide Protects from Lethal Paramyxovirus Infection in a Macrophage- and TLR4-Dependent Process
Jenny Resiliac1,2, Michelle Rohlfing2, Jennifer Santoro2
1The Ohio State University College of Medicine, Biomedical Sciences Graduate Program, Columbus, OH.
Abstract:
Respiratory diseases are a major public health burden and a leading cause of death and disability in the world. Understanding antiviral immune responses is crucial to alleviate morbidity and mortality associated with these respiratory viral infections. Previous data from human and animal studies suggested that pre-existing atopy may provide some protection against severe disease from a respiratory viral infection. However, the mechanism(s) of protection is not understood. Low-dose LPS has been shown to drive an atopic phenotype in mice. In addition, LPS has been shown in vitro to have an antiviral effect. We examined the effect of LPS treatment on mortality to the murine parainfluenza virus Sendai virus. Low-dose LPS treatment 24 h before inoculation with a normally lethal dose of Sendai virus greatly reduced death. This protection was associated with a reduced viral titer and reduced inflammatory cytokine production in the airways. The administration of LPS was associated with a marked increase in lung neutrophils and macrophages. Depletion of neutrophils failed to reverse the protective effect of LPS; however, depletion of macrophages reversed the protective effect of LPS. Further, we demonstrate that the protective effect of LPS depends on type I IFN and TLR4-MyD88 signaling. Together, these studies demonstrate pretreatment with low-dose LPS provides a survival advantage against a severe respiratory viral infection through a macrophage-, TLR4-, and MyD88-dependent pathway.
Insights
Pretreating mice with low-dose lipopolysaccharide (LPS) significantly reduced deaths from respiratory viral infections. This protection involved macrophages and TLR4-MyD88 signaling, offering a potential survival advantage.
Area of Science:
- Immunology
- Respiratory Medicine
- Virology
Background:
- Respiratory diseases pose a significant global health challenge.
- Antiviral immunity is key to managing respiratory viral infections.
- Pre-existing atopy may protect against severe respiratory viral disease, but mechanisms are unclear.
Purpose of the Study:
- To investigate the protective effect of low-dose lipopolysaccharide (LPS) against respiratory viral infection.
- To elucidate the cellular and molecular mechanisms underlying LPS-mediated protection.
Main Methods:
- Mice were pretreated with low-dose LPS before infection with Sendai virus.
- Mortality, viral titers, cytokine production, and immune cell infiltration were assessed.
- Depletion studies were performed for neutrophils and macrophages.
- The role of type I interferon (IFN) and Toll-like receptor 4 (TLR4)-Myeloid differentiation primary response 88 (MyD88) signaling was investigated.
Main Results:
- LPS pretreatment significantly reduced mortality from Sendai virus infection.
- Protection was associated with lower viral titers and reduced airway inflammation.
- LPS increased lung neutrophils and macrophages; macrophage depletion reversed protection.
- The protective effect was dependent on type I IFN and TLR4-MyD88 signaling.
Conclusions:
- Low-dose LPS pretreatment confers a survival advantage against severe respiratory viral infection.
- This protection is mediated by a pathway involving macrophages, TLR4, and MyD88.
- Findings suggest a potential therapeutic strategy for respiratory viral infections.
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