In and out: Leishmania metastasis by hijacking lymphatic system and migrating immune cells

Baijayanti Jha, Marta Reverte, Catherine Ronet, Florence Prevel, Florence D. Morgenthaler, Chantal Desponds, Lon Fye Lye, Katherine L. Owens, Leonardo Scarpellino, Lalit Kumar Dubey, Amélie Sabine, Tatiana V. Petrova, Sanjiv A. Luther, Stephen M. Beverley, Nicolas Fasel

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The lymphatic system plays a crucial role in mounting immune response against intracellular pathogens, and recent studies have documented its role in facilitating tumor dissemination linked largely with cancer cells. However, in mucocutaneous leishmaniasis (MCL) caused by Leishmania Viannia subgenus showing infectious metastasis and resulting in severe distant secondary lesions, the route of escape of these parasites to secondary sites has not yet been investigated in detail. Our results demonstrated that when infection was associated with inflammation and additionally exacerbated by the presence of dsRNA viral endosymbiont (LRV1), lymphatic vessels could serve as efficient routes for infected cells to egress from the primary site and colonize distant organs. We challenged this hypothesis by using the intracellular Leishmania protozoan parasites Leishmania guyanensis (Lgy) associated with or without a dsRNA viral endosymbiont, exacerbating the infection and responsible for a strong inflammatory response, and favoring metastasis of the infection. We analyzed possible cargo cells and the routes of dissemination through flow cytometry, histological analysis, and in vivo imaging in our metastatic model to show that parasites disseminated not only intracellularly but also as free extracellular parasites using migrating immune cells, lymph nodes (LNs), and lymph vessels, and followed intricate connections of draining and non-draining lymph node to finally end up in the blood and in distant skin, causing new lesions.

Original languageEnglish
Article number941860
JournalFrontiers in cellular and infection microbiology
Volume12
DOIs
StatePublished - Aug 12 2022

Keywords

  • Leishmania
  • Leishmania RNA virus 1 (LRV1)
  • dissemination
  • extracellular
  • free amastigotes
  • inflammation
  • lymph nodes (LNs)
  • metastasis

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