THESIS DEFENSE — PUBLIC SEMINAR: SUPPRESSION OF INFLAMMASOME ACTIVATION IN BATS

Start Date & Time: 
Thursday, 11 January, 2018 - 10:00
End Date & Time: 
Thursday, 11 January, 2018 - 11:00
Speaker: 
Speaker Details: 

MATAE AHN
IBM PhD PROGRAM (INTAKE 2013)

Synopsis: 

Bats are special in their ability to host viruses. Many viruses they carry including Ebola virus are highly lethal to humans yet cause minimal clinical signs of disease in bats. As the only flying mammal, bats endure high metabolic rates yet exhibit prolonged lifespans. However, the molecular mechanisms for these observations are totally unknown and it’s currently unclear whether these unique features are inter-linked. Aberrant inflammasome activation leading to excessive systemic inflammation has recently been linked to both viral pathogenesis and multiple age-related diseases. My objective is to characterize the inflammasome activation to gain insights into underlying mechanisms of inflammation control in bats.  Here we investigate the inflammasome activation in bat primary immune cells and cell lines.  Our data show that activation is significantly reduced in bat cells compared to human or mouse counterparts. There is low induction of ASC speck formation, caspase-1 activation and IL-1β secretion in response to various synthetic stimuli and virus infection. Our data suggest at least two molecular mechanisms of this suppression at different steps of the signaling pathway. First, our genome analysis of ten bat species reveals unique loss of the entire PYHIN gene family recognized as the only inflammasome sensors for intracellular DNA. Second, there is reduced function of another important sensor NLRP3 leading to dampened response to ATP, nigericin and infections with Influenza A virus. We identify both novel splice variants and an altered LRR domain of bat NLRP3 as the cause.  Our results elucidate novel and important mechanisms by which bats suppress inflammation with implications for longevity and zoonotic reservoir potential.

 

Thesis Advisor: Prof. Wang Linfa