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Leishmania-induced repression of selected non-coding RNA genes containing B-box element at their promoters in

Anitra L Farrow1, Tanu Rana, Mukul K Mittal

  • 1Department of Microbiology and Immunology, Meharry Medical College, Nashville, TN 37208, USA.

Molecular and Cellular Biochemistry
|December 18, 2010
PubMed

Insights

Leishmania parasites renovate macrophages by down-regulating specific non-coding RNAs in M2 macrophages. This process, involving surface proteins gp63 and LPG, facilitates parasite infection.

Area of Science:

  • Parasitology
  • Immunology
  • Molecular Biology

Background:

  • Leishmania parasites infect host phagocytes, primarily macrophages.
  • Successful Leishmania infection involves macrophage manipulation.
  • M2 macrophages are implicated in supporting parasite growth.

Purpose of the Study:

  • To investigate how Leishmania establishes infection within macrophages.
  • To identify specific molecular mechanisms of macrophage "renovation" by Leishmania.
  • To explore the role of non-coding RNAs in Leishmania-macrophage interactions.

Main Methods:

  • Culturing and polarizing macrophages (M2).
  • Infecting M2 macrophages with Leishmania promastigotes.
  • Analyzing RNA polymerase III (PolIII)-transcribed non-coding RNA (ncRNA) gene expression via RT-qPCR.
  • Assessing the role of Leishmania surface proteins gp63 and LPG.
  • Investigating the transcription factor TFIIIC110 levels.

Main Results:

  • Leishmania growth is supported exclusively by M2 macrophages.
  • Leishmania infection represses specific PolIII-transcribed ncRNAs (7SL, vault, B2 RNA) in M2 macrophages.
  • The B-box binding transcription factor TFIIIC110 is downregulated in infected macrophages.
  • Leishmania surface protease gp63 and glycolipid LPG are essential for ncRNA downregulation.

Conclusions:

  • Leishmania parasites remodel M2 macrophages by repressing B-box containing ncRNA genes.
  • The parasite surface proteins gp63 and LPG cooperate to downregulate TFIIIC110.
  • This downregulation of TFIIIC110 and subsequent ncRNA repression is crucial for Leishmania establishment within M2 macrophages.

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