Macrophages induce neutrophil apoptosis through membrane TNF, a process amplified by Leishmania major

Area of Science:

• Immunology
• Parasitology
• Cell Biology

Background:

• Neutrophils rapidly infiltrate sites of Leishmania major infection.
• Neutrophil persistence differs between resistant (C57BL/6) and susceptible (BALB/c) mice.
• The role of macrophages in regulating neutrophil lifespan during infection is unclear.

Purpose of the Study:

• To investigate the role of macrophages (MPhi) in controlling neutrophil numbers.
• To elucidate the mechanism by which MPhi influence neutrophil apoptosis.
• To determine the involvement of Tumor Necrosis Factor (TNF) in MPhi-mediated neutrophil apoptosis.

Main Methods:

• Recruitment of inflammatory cells using starch or Leishmania major promastigotes.
• Isolation and co-culture of neutrophils with varying numbers of MPhi.
• Assessment of neutrophil apoptosis using MPhi from wild-type, TNF-deficient, and membrane TNF knock-in mice.
• Transwell chamber assays to evaluate the necessity of cell contact.

Main Results:

• Macrophage presence significantly increased neutrophil apoptosis in a dose-dependent manner.
• Macrophage-induced neutrophil apoptosis was strictly dependent on TNF, specifically membrane-bound TNF.
• Cell-to-cell contact between MPhi and neutrophils was required for apoptosis induction.
• Leishmania major infection enhanced MPhi-induced neutrophil apoptosis, with C57BL/6 MPhi being more potent than BALB/c MPhi.

Conclusions:

• Macrophage-induced neutrophil apoptosis, mediated by membrane TNF, plays a critical role in early inflammation control during Leishmania major infection.
• Differences in MPhi function may contribute to varying resistance levels observed in different mouse strains.
• Targeting MPhi-membrane TNF interactions could be a strategy for managing parasitic infections.