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Eosinophils induce DC maturation, regulating immunity.

Ramin Lotfi1, Michael Thomas Lotze

  • 1Surgery and Bioengineering, Hillmann Cancer Center, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.

Journal of Leukocyte Biology
|November 10, 2007
PubMed
Summary
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CpG DNA activates eosinophils to mature dendritic cells (DCs), suggesting a link between innate immune cells and adaptive immunity. This eosinophil-induced DC maturation may involve the release of major basic protein (MBP).

Area of Science:

  • Immunology
  • Innate and Adaptive Immunity
  • Cellular Interactions

Background:

  • Eosinophils in tumors often indicate a good prognosis, contrasting with their role in allograft rejection. The precise function of eosinophils in pathogenesis, beyond allergy and asthma, remains unclear.
  • Conventional dendritic cells (DCs) are linked to favorable outcomes in cancer patients, similar to eosinophils in tumors.

Purpose of the Study:

  • To investigate the hypothesis that eosinophils can mature dendritic cells (DCs), potentially regulating immunity in chronic inflammation settings like cancer and transplant rejection.
  • To explore the role of CpG DNA in mediating eosinophil-induced DC maturation and the underlying mechanisms.

Main Methods:

  • Isolation of human granulocytes and eosinophils, and generation of immature DCs from monocytes.

Related Experiment Videos

  • Co-culture of eosinophils and DCs with CpG ODN 2395 (CpG-C) to induce maturation, utilizing Transwell systems to assess cell-cell interactions.
  • Analysis of eosinophil survival, DC maturation markers, and uptake of eosinophil-derived proteins (e.g., MBP) via flow cytometry and confocal imaging.

    • Main Results:

    • CpG-C stimulation induced eosinophil-mediated maturation of conventional DCs, with maturation correlating to the eosinophil:DC ratio.
    • Direct cell-cell contact between eosinophils and DCs enhanced DC maturation, and CpG did not compromise eosinophil viability.
    • Major basic protein (MBP) released from CpG-stimulated eosinophils was internalized by DCs, suggesting it mediates the observed DC maturation effect.

    Conclusions:

    • CpG-activated eosinophils can mature conventional DCs, establishing a connection between innate immune cells and adaptive immune responses.
    • The release of MBP from activated eosinophils appears to be a key mechanism driving DC maturation.
    • Further research should explore the role of various activators, including pathogen-associated molecular patterns and host-derived DNA, in eosinophil-mediated DC maturation within inflammatory contexts.