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.

Nature Immunology
|March 29, 2001
PubMed

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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