Cutting edge: neutrophil granulocyte serves as a vector for Leishmania entry into macrophages

Ger van Zandbergen1, Matthias Klinger, Antje Mueller

  • 1Institute for Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany. Zandbergen@hygiene.ukl.mu-luebeck.de

Insights

Leishmania parasites infect neutrophils (PMN), delaying their death and causing them to attract macrophages (MF). Macrophages then ingest these infected neutrophils, allowing Leishmania to enter and multiply within them.

Area of Science:

  • Immunology
  • Parasitology
  • Cell Biology

Background:

  • Macrophages (MF) are the primary host cells for Leishmania major (L. major) replication.
  • Polymorphonuclear neutrophil granulocytes (PMN) are the initial leukocytes at infection sites, encountering L. major before MF.
  • Previous research showed PMN phagocytose but do not eliminate L. major, with infected PMN apoptosis delayed for 2 days.

Purpose of the Study:

  • To investigate if macrophages can ingest Leishmania-infected neutrophils.
  • To understand the mechanism by which Leishmania utilizes PMN for host cell entry.

Main Methods:

  • Co-culture of Leishmania-infected neutrophils with macrophages.
  • Observation of phagocytosis of infected neutrophils by macrophages.
  • Analysis of Leishmania survival and multiplication within macrophages.
  • Measurement of cytokine release (TGF-beta) from macrophages post-phagocytosis.

Main Results:

  • Macrophages readily phagocytosed Leishmania-infected apoptotic neutrophils.
  • Leishmania survived and multiplied within macrophages after indirect internalization via neutrophils.
  • Ingestion of infected neutrophils by macrophages induced the release of the anti-inflammatory cytokine TGF-beta.

Conclusions:

  • Leishmania major exploits neutrophils as a "Trojan horse" to facilitate entry into macrophages.
  • This mechanism allows Leishmania to enter its final host cells undetected.
  • The process involves delayed neutrophil apoptosis, chemokine secretion, and subsequent macrophage phagocytosis.

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