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Interactions with apoptotic but not with necrotic neutrophils increase parasite burden in human macrophages infected

Lilian Afonso1, Valéria M Borges, Heloísa Cruz

  • 1Centro de Pesquisas Gonçalo Moniz-Fundação Oswaldo Cruz (CPqGM)- Fundação Oswaldo Cruz (FIOCRUZ), Salvador-BA, 40295-001, Brazil.

Journal of Leukocyte Biology
|May 17, 2008
PubMed

Insights

The way macrophages interact with dying neutrophils impacts Leishmania amazonensis infection. Apoptotic neutrophils increase parasite burden, while necrotic neutrophils promote parasite killing through specific molecular pathways.

Area of Science:

  • Immunology
  • Cell Biology
  • Parasitology

Background:

  • Neutrophils are crucial in early host defense against pathogens.
  • The interaction between immune cells and neutrophils in different states of cell death can significantly alter infection outcomes.

Purpose of the Study:

  • To investigate how apoptotic versus necrotic human neutrophils affect macrophage infection by Leishmania amazonensis.
  • To elucidate the molecular mechanisms underlying these interactions.

Main Methods:

  • Co-culture of Leishmania-infected macrophages with either apoptotic or necrotic human neutrophils.
  • Analysis of parasite burden, cytokine production (TGF-beta1, PGE2, TNF-alpha), and reactive oxygen species (ROS) generation.

Main Results:

  • Phagocytosis of apoptotic neutrophils by infected macrophages increased Leishmania burden, mediated by TGF-beta1 and PGE2.
  • Uptake of necrotic neutrophils by infected macrophages led to parasite killing, dependent on TNF-alpha and neutrophilic elastase.
  • Necrotic neutrophil interaction induced high superoxide production, inhibited by catalase, indicating a role for ROS.

Conclusions:

  • The state of neutrophil cell death (apoptotic vs. necrotic) critically influences the host's ability to control Leishmania amazonensis infection.
  • Distinct molecular pathways involving cytokines and ROS mediate the differential effects of apoptotic and necrotic neutrophils on macrophage anti-parasitic activity.

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