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Isolation of Peritoneum-derived Mast Cells and Their Functional Characterization with Ca2+-imaging and Degranulation Assays
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Dengue vascular leakage is augmented by mast cell degranulation mediated by immunoglobulin Fcγ receptors

Ayesa Syenina1, Cyril J Jagaraj1, Siti A B Aman1

  • 1Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, Singapore.

Elife
|March 19, 2015
PubMed

Insights

Secondary dengue virus (DENV) infections cause severe vascular leakage. Mast cells, activated by antibodies, drive this leakage through FcγR-mediated degranulation, revealing a new mechanism for severe dengue.

Area of Science:

  • Virology
  • Immunology
  • Pathology

Background:

  • Dengue virus (DENV) is a major global arboviral pathogen causing significant human infections annually.
  • Mast cells (MC) are implicated in mediating vascular leakage during DENV infection, with activation levels correlating with disease severity in humans.
  • Secondary DENV infections with heterologous serotypes increase the risk of severe dengue.

Purpose of the Study:

  • To investigate mechanisms underlying enhanced vascular leakage during secondary DENV infections.
  • To explore the role of mast cells and antibody-dependent activation in severe dengue pathogenesis.

Main Methods:

  • The study focused on FcγR-mediated mast cell degranulation responses.
  • Investigated antibody-dependent mast cell activation as a potential mechanism for enhanced vascular leakage.

Main Results:

  • A novel mechanism involving FcγR-mediated enhanced degranulation responses by mast cells was identified.
  • Antibody-dependent mast cell activation was shown to contribute to enhanced vascular leakage.

Conclusions:

  • Antibody-dependent mast cell activation presents a new mechanism explaining increased vascular leakage in secondary DENV infections.
  • This finding offers a novel perspective on the pathogenesis of severe dengue.
Keywords:
Fc receptorantibodiesdengue virusimmunologyinfectious diseasemast cellmicrobiologymousevascular leakage

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