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* World Health Organization (WHO) Immunology Research and Training Center, Department of Biochemistry, Epalinges, Switzerland; and
Department of Pathology, University of Bern, Bern, Switzerland
Neutrophils are recruited to the site of parasite inoculation within a few hours of infection with the protozoan parasite Leishmania major. In C57BL/6 mice, which are resistant to infection, neutrophils are cleared from the site of s.c. infection within 3 days, whereas they persist for at least 10 days in susceptible BALB/c mice. In the present study, we investigated the role of macrophages (M
) in regulating neutrophil number. Inflammatory cells were recruited by i.p. injection of either 2% starch or L. major promastigotes. Neutrophils were isolated and cultured in the presence of increasing numbers of M. Extent of neutrophil apoptosis positively correlated with the number of M added. This process was strictly dependent on TNF because M from TNF-deficient mice failed to induce neutrophil apoptosis. Assays using M derived from membrane TNF knock-in mice or cultures in Transwell chambers revealed that contact with M was necessary to induce neutrophil apoptosis, a process requiring expression of membrane TNF. L. major was shown to exacerbate M-induced apoptosis of neutrophils, but BALB/c M were not as potent as C57BL/6 M in this induction. Our results emphasize the importance of M-induced neutrophil apoptosis, and membrane TNF in the early control of inflammation.
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