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Mast Cell Activation Triggered by Retrovirus Promotes Acute Viral Infection

Shu-Ting Song1,2, Meng-Li Wu3,4, Hai-Jiao Zhang5

  • 1Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.

Frontiers in Microbiology
|February 24, 2022
PubMed

Insights

Mast cells (MCs) promote retroviral infection by suppressing antiviral immunity. Blocking MC degranulation enhances immune responses and controls infection, suggesting MCs as a therapeutic target.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Mast cells (MCs) are increasingly recognized for non-allergic roles in pathogen surveillance.
  • Their involvement in retroviral infections, particularly HIV-1 and murine leukemia virus (MuLV), is not fully understood.
  • Previous research suggests MCs can facilitate HIV-1 spread and induce immunosuppression.

Purpose of the Study:

  • To investigate the role of mast cells in acute retroviral infection using a murine model.
  • To elucidate the underlying immune mechanisms by which mast cells influence retroviral pathogenesis.
  • To explore mast cell-targeted interventions for controlling retroviral infections.

Main Methods:

  • Utilized a murine model of Friend virus (MuLV) infection in wild-type and mast cell-deficient (Sash) mice.
  • Analyzed viral acquisition, mast cell activation (degranulation), and immune cell responses (CD8+ T cells, NK cells, G-MDSCs).
  • Investigated the effect of mast cell stabilization on retroviral infection and antiviral immunity.

Main Results:

  • Mast cell-deficient mice exhibited significantly lower viral acquisition compared to wild-type mice.
  • Friend virus infection triggered mast cell degranulation, which activated granulocyte-like myeloid-derived suppressive cells (G-MDSCs).
  • Activated G-MDSCs inhibited CD8+ T cell and NK cell antiviral responses, promoting viral infection. Conversely, mast cell stabilization enhanced antiviral immunity and suppressed infection.

Conclusions:

  • Mast cells play a critical role in promoting acute retroviral infection by suppressing antiviral immune responses via G-MDSC activation.
  • Targeting mast cell degranulation represents a potential therapeutic strategy for controlling acute retroviral infections.
  • This study reveals novel immune mechanisms underlying mast cell involvement in retroviral pathogenesis.
Keywords:
MDSC (myeloid-derived suppressor cell)acute infectiondegranulationmast cellretrovirus

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