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The Journal of Immunology, 2004, 173: 6521-6525.
Copyright © 2004 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Neutrophil Granulocyte Serves as a Vector for Leishmania Entry into Macrophages1

Ger van Zandbergen2,*, Matthias Klinger{ddagger}, Antje Mueller{dagger}, Sonja Dannenberg*, Andreas Gebert{ddagger}, Werner Solbach* and Tamás Laskay*

* Institute for Medical Microbiology and Hygiene, {dagger} Clinic for Rheumatology, and {ddagger} Institute for Anatomy, University of Lübeck, Lübeck, Germany

Macrophages (MF) are the final host cells for multiplication of the intracellular parasite Leishmania major (L. major). However, polymorphonuclear neutrophil granulocytes (PMN), not MF, are the first leukocytes that migrate to the site of infection and encounter the parasites. Our previous studies indicated that PMN phagocytose but do not kill L. major. Upon infection with Leishmania, apoptosis of human PMN is delayed and takes 2 days to occur. Infected PMN were found to secrete high levels of the chemokine MIP-1{beta}, which attracts MF. In this study, we investigated whether MF can ingest parasite-infected PMN. We observed that MF readily phagocytosed infected apoptotic PMN. Leishmania internalized by this indirect way survived and multiplied in MF. Moreover, ingestion of apoptotic infected PMN resulted in release of the anti-inflammatory cytokine TGF-{beta} by MF. These data indicate that Leishmania can misuse granulocytes as a "Trojan horse" to enter their final host cells "silently" and unrecognized.




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