8 research outputs found
2D sejtmozgás és vírusterjedés in vitro valamint 3D kollektív mozgás in silico statisztikus fizikája
Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms
Neurotropic herpesviruses can establish lifelong infection in humans and contribute to severe diseases including encephalitis and neurodegeneration. However, the mechanisms through which the brain's immune system recognizes and controls viral infections propagating across synaptically linked neuronal circuits have remained unclear. Using a well-established model of alphaherpesvirus infection that reaches the brain exclusively via retrograde transsynaptic spread from the periphery, and in vivo two-photon imaging combined with high resolution microscopy, we show that microglia are recruited to and isolate infected neurons within hours. Selective elimination of microglia results in a marked increase in the spread of infection and egress of viral particles into the brain parenchyma, which are associated with diverse neurological symptoms. Microglia recruitment and clearance of infected cells require cell-autonomous P2Y12 signalling in microglia, triggered by nucleotides released from affected neurons. In turn, we identify microglia as key contributors to monocyte recruitment into the inflamed brain, which process is largely independent of P2Y12. P2Y12-positive microglia are also recruited to infected neurons in the human brain during viral encephalitis and both microglial responses and leukocyte numbers correlate with the severity of infection. Thus, our data identify a key role for microglial P2Y12 in defence against neurotropic viruses, whilst P2Y12-independent actions of microglia may contribute to neuroinflammation by facilitating monocyte recruitment to the sites of infection
Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms
Neurotropic herpesviruses can establish lifelong infection in humans and contribute to severe diseases including encephalitis and neurodegeneration. However, the mechanisms through which the brain's immune system recognizes and controls viral infections propagating across synaptically linked neuronal circuits have remained unclear. Using a well-established model of alphaherpesvirus infection that reaches the brain exclusively via retrograde transsynaptic spread from the periphery, and in vivo two-photon imaging combined with high resolution microscopy, we show that microglia are recruited to and isolate infected neurons within hours. Selective elimination of microglia results in a marked increase in the spread of infection and egress of viral particles into the brain parenchyma, which are associated with diverse neurological symptoms. Microglia recruitment and clearance of infected cells require cell-autonomous P2Y12 signalling in microglia, triggered by nucleotides released from affected neurons. In turn, we identify microglia as key contributors to monocyte recruitment into the inflamed brain, which process is largely independent of P2Y12. P2Y12-positive microglia are also recruited to infected neurons in the human brain during viral encephalitis and both microglial responses and leukocyte numbers correlate with the severity of infection. Thus, our data identify a key role for microglial P2Y12 in defence against neurotropic viruses, whilst P2Y12-independent actions of microglia may contribute to neuroinflammation by facilitating monocyte recruitment to the sites of infection
Viral epidemics in a cell culture: novel high resolution data and their interpretation by a percolation theory based model
Because of its relevance to everyday life, the spreading of viral infections
has been of central interest in a variety of scientific communities involved in
fighting, preventing and theoretically interpreting epidemic processes. Recent
large scale observations have resulted in major discoveries concerning the
overall features of the spreading process in systems with highly mobile
susceptible units, but virtually no data are available about observations of
infection spreading for a very large number of immobile units. Here we present
the first detailed quantitative documentation of percolation-type viral
epidemics in a highly reproducible in vitro system consisting of tens of
thousands of virtually motionless cells. We use a confluent astroglial
monolayer in a Petri dish and induce productive infection in a limited number
of cells with a genetically modified herpesvirus strain. This approach allows
extreme high resolution tracking of the spatio-temporal development of the
epidemic. We show that a simple model is capable of reproducing the basic
features of our observations, i.e., the observed behaviour is likely to be
applicable to many different kinds of systems. Statistical physics inspired
approaches to our data, such as fractal dimension of the infected clusters as
well as their size distribution, seem to fit into a percolation theory based
interpretation. We suggest that our observations may be used to model epidemics
in more complex systems, which are difficult to study in isolation.Comment: To appear in PLoS ONE. Supporting material can be downloaded from
http://amur.elte.hu/BDGVirus