Down-regulation of 7SL RNA expression and impairment of vesicular protein transport pathways by Leishmania infection of macrophages

Smita Misra, Manish Tripathi, Gautam Chaudhuri

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The parasitic protozoan Leishmania specifically manipulates the expression of host macrophage genes during initial interactions, as revealed by mRNA differential display reverse transcription-PCR and cDNA microarray analyses. The genes that are down-regulated in mouse (J774G8) or human (U937) macrophages upon exposure to Leishmania include small RNA transcripts from the short interspersed element sequences. Among the short interspersed element RNAs that are down-regulated is 7SL RNA, which is the RNA component of the signal recognition particle. Because the microbicidal functions of macrophages profoundly count on vesicular protein transport processes, down-regulation of 7SL RNA may be significant in the establishment of infection by Leishmania in macrophage phagolysosomes. To evaluate whether down-regulation of 7SL RNA results in inhibition of signal recognition particle-mediated vesicular protein transport processes, we have tested and found that the targeting of proteins to the endoplasmic reticulum and plasma membrane and the secretion of proteins by macrophages are compromised in Leishmania-infected J774G8 and U937 cells. Knocking down 7SL RNA using small interfering RNA mimicked the effect of exposure of macrophages to Leishmania. The overexpression of 7SL RNA in J774G8 or U937 cells made these cells resistant to Leishmania infection, suggesting the possible biological significance of down-regulation of 7SL RNA synthesis in the establishment of infection by Leishmania. We conclude that Leishmania down-regulates 7SL RNA in macrophages to manipulate the targeting of many proteins that use the vesicular transport pathway and thus favors its successful establishment of infection in macrophages.

Original languageEnglish (US)
Pages (from-to)29364-29373
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number32
DOIs
StatePublished - Aug 12 2005

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Macrophages
Leishmania
Protein Transport
Down-Regulation
Infection
Proteins
Signal Recognition Particle
U937 Cells
RNA
Genes
Phagosomes
7SL RNA
Gene Expression Profiling
Transcription
Cell membranes
Microarray Analysis
Microarrays
Oligonucleotide Array Sequence Analysis
Endoplasmic Reticulum
Small Interfering RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Down-regulation of 7SL RNA expression and impairment of vesicular protein transport pathways by Leishmania infection of macrophages. / Misra, Smita; Tripathi, Manish; Chaudhuri, Gautam.

In: Journal of Biological Chemistry, Vol. 280, No. 32, 12.08.2005, p. 29364-29373.

Research output: Contribution to journalArticle

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