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Leishmania expressed lipophosphoglycan interacts with Toll-like receptor (TLR)-2 to decrease TLR-9 expression and

S Srivastava1, S P Pandey, M K Jha

  • 1National Centre for Cell Science, Pune, India.

Clinical and Experimental Immunology
|April 23, 2013
PubMed
Summary

Lipophosphoglycan (LPG) interaction with Toll-like receptor-2 (TLR-2) on macrophages decreases Toll-like receptor-9 (TLR-9) expression, impairing host defense against Leishmania parasites. Blocking LPG-TLR-2 interaction restores anti-leishmanial responses.

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Area of Science:

  • Immunology
  • Parasitology
  • Molecular Biology

Background:

  • Toll-like receptors (TLRs) modulate host responses to Leishmania infection.
  • TLR-2 activation by Leishmania lipophosphoglycan (LPG) promotes parasite survival.
  • TLR-9 activation typically induces a host-protective immune response.

Purpose of the Study:

  • To investigate the relationship between LPG-TLR-2 interaction and TLR-9 expression in Leishmania infection.
  • To elucidate the mechanisms by which LPG affects TLR-9 expression and anti-leishmanial immunity.

Main Methods:

  • In vitro infection of macrophages with Leishmania major parasites exhibiting differential LPG expression.
  • Treatment with anti-LPG and anti-TLR-2 antibodies, purified LPG, and cytokines (TGF-β, IL-10).
  • In vivo studies involving antibody treatment in infected mice and assessment of immune responses (footpad swelling, parasite load, T cell response).

Main Results:

  • Leishmania infection with high LPG expression reduced macrophage TLR-9 expression, an effect prevented by anti-LPG/anti-TLR-2 antibodies.
  • Purified LPG decreased TLR-9 expression via TGF-β and IL-10.
  • Blocking LPG-TLR-2 interaction reduced parasite burden in vitro and in vivo, enhancing host-protective immunity (IFN-γ response).

Conclusions:

  • Leishmania LPG interaction with TLR-2 downregulates TLR-9 expression, contributing to parasite persistence.
  • This LPG-TLR-2-mediated suppression of TLR-9 is cytokine-dependent.
  • Targeting the LPG-TLR-2 pathway enhances anti-leishmanial immunity and represents a potential therapeutic strategy.