Dr. Marlena Westcott Research Interests
Dendritic cells (DC) of the innate immune system are a
heterogeneous group of cells that are essential for activating adaptive
immunity. DC are among the first cells
to sense pathogens and are thus highly adapted to translating pathogenic
signals into a response, termed maturation, that leads to an adaptive immune
response that is appropriate for eliminating the invading pathogen. In order to induce a pathogen-neutralizing
immune response, DC must be able to function even when confronted with pathogens
that have evolved subversive mechanisms.
My interest is in understanding the detailed interactions between DC and
bacterial and viral pathogens, that promote DC maturation, and by extension,
the development of an effective immune response. My studies utilize two model pathogens, Listeria monocytogenes, a Gram-positive
facultative intracellular bacterium, and Vesicular Stomatitis Virus (VSV), a
prototypic negative strand RNA virus, to address this question.
Both Listeria
monocytogenes and VSV have developed strategies that allow them to grow and
spread within DC populations. One
project involves understanding how DC mature when infected with w.t. VSV. This virus produces a protein (“M”) that
effectively shuts down host gene expression and protein production in a wide
range of cell types. One specific type
of in vitro-propagated DC,
representative of resident splenic populations in mice, is able to mature even
in the presence of M protein. The
molecular events that allow for DC maturation under these circumstances is one
topic of study.
Another project involves a host factor common to
the two models that we have discovered recently. Both
Listeria
and VSV induce a different subclass of DC to express high levels of a gene
that encodes an enzyme that modifies cholesterol. The modified product, 25-hydroxycholesterol,
has recently reported immunosuppressive properties. The influence of this cholesterol metabolite
on DC maturation and activation of adaptive immunity is another current area of
investigation.