ER-Coordinated Activities of Rab22a and Rab5a Drive Phagosomal Compaction and Intracellular Processing of Borrelia burgdorferi by Macrophages

Cell Rep. 2015 Sep 22;12(11):1816-30. doi: 10.1016/j.celrep.2015.08.027. Epub 2015 Sep 3.


Borrelia burgdorferi is the causative agent of Lyme disease, a multisystemic disorder affecting the skin, joints, and nervous system. Macrophages and dendritic cells counteract Borrelia dissemination through internalization and degradation of spirochetes. We now show that Borrelia internalization by primary human macrophages involves uptake and compaction into Rab22a-positive phagosomes that are in close contact with Rab5a-positive vesicles. Compaction of borreliae involves membrane extrusion from phagosomes, is driven by Rab22a and Rab5a activity, and is coordinated by ER tubules forming contact sites of Rab22a phagosomes with Rab5a vesicles. Importantly, Rab22a and Rab5a depletion leads to reduced localization to lysosomes and to increased intracellular survival of spirochetes. These data show that Rab22a- and Rab5a-driven phagosomal uptake is a crucial step in the vesicular cascade that leads to elimination of spirochetes by macrophages. Rab22a and Rab5a thus present as potential molecular targets for the modulation of intracellular processing of borreliae in human immune cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Borrelia burgdorferi / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / microbiology
  • Humans
  • Lyme Disease / metabolism*
  • Lyme Disease / microbiology
  • Lysosomes / microbiology
  • Macrophages / metabolism*
  • Macrophages / microbiology
  • Phagocytosis
  • Transfection
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*
  • rab5 GTP-Binding Proteins / genetics
  • rab5 GTP-Binding Proteins / metabolism*


  • RAB22A protein, human
  • RAB5C protein, human
  • rab GTP-Binding Proteins
  • rab5 GTP-Binding Proteins