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* Institute for Medical Microbiology and Hygiene and
Institute for Physiology, Medical University of Lübeck, Lübeck, Germany
Macrophages are the major target cell population of the obligate
intracellular parasites Leishmania. Although
polymorphonuclear neutrophil granulocytes (PMN) are able to internalize
Leishmania promastigotes, these cells have not been
considered to date as host cells for the parasites, primarily due to
their short life span. In vitro coincubation experiments were conducted
to investigate whether Leishmania can modify the
spontaneous apoptosis of human PMN. Coincubation of PMN with
Leishmania major promastigotes resulted in a significant
decrease in the ratio of apoptotic neutrophils as detected by
morphological analysis of cell nuclei, TUNEL assay, gel electrophoresis
of low m.w. DNA fragments, and annexin V staining. The observed
antiapoptotic effect was found to be associated with a significant
reduction of caspase-3 activity in PMN. The inhibition of PMN apoptosis
depended on viable parasites because killed Leishmania
or a lysate of the parasites did not have antiapoptotic effect.
L. major did not block, but rather delayed the
programmed cell death of neutrophils by 
24 h. The antiapoptotic
effect of the parasites could not be transferred by the supernatants,
despite secretion of IL-8 by PMN upon coculture with L.
major. In vivo, intact parasites were found intracellularly in
PMN collected from the skin of mice 3 days after s.c. infection. This
finding strongly suggests that infection with Leishmania
prolongs the survival time of neutrophils also in vivo. These data
indicate that Leishmania induce an increased survival of
neutrophil granulocytes both in vitro and in vivo.
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