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.

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Microbiology & Immunology
Wake Forest School of Medicine
Medical Center Boulevard
Winston-Salem, NC 27157
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Last Updated: 12-04-2013
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