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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism
C Werts1, R I Tapping, J C Mathison
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Abstract:
Leptospira interrogans are zoonotic pathogens that have been linked to a recent increased incidence of morbidity and mortality in highly populated tropical urban centers. They are unique among invasive spirochetes in that they contain outer membrane lipopolysaccharide (LPS) as well as lipoproteins. Here we show that both these leptospiral outer membrane constituents activate macrophages through CD14 and the Toll-like receptor 2 (TLR2). Conversely, it seems that TLR4, a central component for recognition of Gram-negative LPS, is not involved in cellular responses to L. interrogans. We also show that for intact L. interrogans, it is LPS, not lipoprotein, that constitutes the predominant signaling component for macrophages through a TLR2 pathway. These data provide a basis for understanding the innate immune response caused by leptospirosis and demonstrate a new ligand specificity for TLR2.
Insights
Leptospira interrogans outer membrane components, lipopolysaccharide (LPS) and lipoproteins, activate macrophages via Toll-like receptor 2 (TLR2). LPS is the primary signaling molecule, not TLR4, in this innate immune response.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Leptospira interrogans are zoonotic pathogens causing increased illness and death in tropical urban areas.
- These spirochetes possess unique outer membrane components: lipopolysaccharide (LPS) and lipoproteins.
Purpose of the Study:
- To investigate how L. interrogans outer membrane components activate macrophages.
- To determine the roles of Toll-like receptor 2 (TLR2) and TLR4 in the cellular response to L. interrogans.
Main Methods:
- Macrophage activation assays using L. interrogans outer membrane constituents.
- Analysis of cellular signaling pathways involving CD14, TLR2, and TLR4.
Main Results:
- Both LPS and lipoproteins from L. interrogans activate macrophages through CD14 and TLR2.
- Toll-like receptor 4 (TLR4) is not involved in the cellular response to L. interrogans.
- For intact L. interrogans, LPS is the predominant signaling component activating macrophages via TLR2.
Conclusions:
- Leptospiral LPS and lipoproteins are key activators of the innate immune response through TLR2.
- This study reveals a novel ligand specificity for TLR2 in the context of leptospirosis.
- Findings provide a foundation for understanding leptospirosis pathogenesis and immune evasion.
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