Mast Cell Response to Influenza A Infection and Their Antiviral Activity in Co-culture with Epithelial Cells

  • Author / Creator
    Ng, Kurtis WC
  • Well known their role in allergic inflammation, mast cells (MC) are also important in innate immunity against pathogens. MC are abundant in the respiratory tract and in close proximity to epithelial cells (EC) where they could be important in host defenses or the pathogenesis of viral infections such as with influenza A (FluA). However, little is known about the roles of MC in viral infections of the airways.
    To investigate, the potential role of MC in FluA infections, we measured short-term mediator release of MC and found that they release histamine, β-hexosaminidase and prostaglandin D2 following exposure to selected strains of FluA. Of several cytokines and chemokines studied, MC only released CCL-4 after FluA exposure, whereas EC released CCL-5, CXCL-10 and type III interferon. Since it was previously shown that following FluA infection, MC produce few new FluA progeny, we investigated expression of selected antiviral genes in MC and EC at several different time points. FluA exposure induced the expression of RIG-I and MDA5 mRNA in MC, but only Viperin in EC. Neither EC nor MC had increased expression of MAVS mRNA.
    We co-cultured FluA-exposed EC with or without MC. When MC were present, FluA release from EC was decreased. In co-culture, this was associated with increased release of Flt-3L and CCL-4. We also determined that bottom chamber supernatants from co-cultures with FluA-exposed EC inhibited FluA release from EC. Heat treatment (100°C) and protease digestion eliminated the antiviral activity in supernatants derived from MC. We determined the molecular size of the antiviral activity to be greater than 10 kDa and to have a relatively strong positive charge with a weak negative charge. Preliminary results from mass spectrometric studies of MC-derived antiviral supernatants showed strong signals of keratin. Despite not precisely identifying the nature of the antiviral activity, we gained a better understanding of MC in antiviral immunity and their collaboration with EC.  

  • Subjects / Keywords
  • Graduation date
    Fall 2018
  • Type of Item
  • Degree
    Master of Science
  • DOI
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