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Leishmania-induced repression of selected non-coding RNA genes containing B-box element at their promoters in alternatively polarized M2 macrophages

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Abstract

Leishmania is a group of parasitic protozoa that infect blood and tissue phagocytes including macrophages. We hypothesize that Leishmania is capable of establishing infection inside the macrophages because (a) they infect a subpopulation of macrophages; and (b) they “renovate” the macrophages before the establishment of infection. We found that only alternatively activated polarized M2 macrophages support Leishmania growth. Exposure of M2 macrophages to Leishmania promastigotes represses several selected RNA polymerase III (PolIII)-transcribed non-coding RNA (ncRNA) genes including those of 7SL RNA, vault RNA, and B2 RNA which have B-box element at their promoters. The B-box-binding transcription factor TFIIIC110 is down-regulated in Leishmania-exposed macrophages. Both the surface protease gp63 and the surface glycolipid LPG are required for the down-regulation of the ncRNAs in the M2 macrophages. We conclude that Leishmania surface gp63 collaborates with LPG to down-regulate TFIIIC110 in M2 macrophages to repress B-box containing ncRNA gene promoters.

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Acknowledgments

This project is supported in parts by NIAID grants 5R01AI042327, 1R21AI076757-01A1 and NIGMS grant #3 S06 GM008037-34-S2 to GC. Graduate student stipend is provided to ALF from the institutional training grants 2T32AI007281-21A1 and 5R25GM059994-10 from NIH.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Meharry Medical College, 1005 D. B. Todd Jr. Blvd, Nashville, TN, 37208, USA

    Anitra L. Farrow, Tanu Rana, Mukul K. Mittal, Smita Misra & Gautam Chaudhuri

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  1. Anitra L. Farrow
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  2. Tanu Rana
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  3. Mukul K. Mittal
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Correspondence to Gautam Chaudhuri.

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Farrow, A.L., Rana, T., Mittal, M.K. et al. Leishmania-induced repression of selected non-coding RNA genes containing B-box element at their promoters in alternatively polarized M2 macrophages. Mol Cell Biochem 350, 47–57 (2011). https://doi.org/10.1007/s11010-010-0681-5

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