Julie Swartzendruber, Ph.D.

Assistant Professor


Midwestern University profile
Chicago College of Osteopathic Medicine
Department of Microbiology and Immunology 
Science Hall 323-K

555 31st St.
Downers Grove, IL 60515

Office: (630) 515-7315
e-mail: mailto:jswart@midwestern.edu

EDUCATION

Ph.D. Biological Life Sciences Northwestern University 2013
B.A. Biochemistry/Biology Wartburg College 2007

RESEARCH SUMMARY

The incidence of food allergy is on the rise and a proposed explanation is a loss of tolerance due to altered commensal bacteria.  We have found a bacterial product, exopolysaccharide (EPS), produced by the bacterium Bacillus subtilis that can prevent allergic sensitization in a murine model of food allergy and prevent mast cell activation in vitro.   The hygiene hypothesis, initially proposed by Strachan in 1989 to explain the rising incidence of hay fever, describes the importance of early life exposure to microbes and their role in shaping the development of the immune system.    It is becoming widely appreciated that commensal bacteria are important in shaping health and recent theories suggest that an absence of gut microbes results in impaired immune toleranceThe goal of my work is to determine the mechanism by which the Gram-positive spore forming bacterium Bacillus subtilis suppresses the immune system to prevent the development of allergic disease.  This work is performed in collaboration with Dr. Katherine Knight at Loyola University of Chicago.

Project I: Determine mechanism by which EPS prevents allergic sensitization

Allergic sensitization results in the generation of antigen-specific IgE, which is initiated by dendritic cell presentation of antigen-specific peptide to T helper cells. In allergic disease, IL-4 and IL-13 polarize this interaction to promote the development of T helper type 2 cells, which interact with B cells and promote isotype class switching to IgE, as well as to IgG1.  Our preliminary data shows that injection of EPS can prevent sensitization to ovalbumin (OVA) in a murine model of allergy.  EPS could prevent allergic sensitization by anergizing T helper cells, promoting T regulatory cells, or by preventing polarization of naïve CD4 cells to T helper type 2 cells. 

This project will involve working with murine dendritic cells and T cells in tissue culture and measuring dendritic cell and T cell surface marker expression and proliferation using flow cytometry.

Project II: Determine the mechanism for EPS prevention of mast cell activation

Anaphylaxis in response to food allergens such as peanuts is a serious health-risk with a need for better treatment options.  Our preliminary data has identified that EPS can suppress mast cell activation in vitro.  Mast cells are the hallmark cell that elicits the signaling cascade that results in symptoms of allergic anaphylaxis. The goal of this project is to determine the mechanism by which EPS prevents mast cell activation.  First we will determine if EPS prevents mast cell activation by suppressing signaling through the high affinity IgE receptor, FcER1.  FcER1 expression is essential for binding to allergen-specific IgE and subsequent crosslinking and mast cell degranulation.  Secondly, we will determine if EPS treatment promotes mast cell apoptosis.  In the event that mast cell numbers are depleted the symptoms of allergy would be suppressed.  Thirdly, we will test if EPS treatment induces piecemeal degranulation of mast cells.  Anaphylactic degranulation of mast cells is characterized by massive and complete release of inflammatory granules from mast cells. 

This project will involve working with murine mast cells in tissue culture and measuring mast cell activation using microscopy, flow cytometry, and ELISAs.

Selected Publications:

Cutting edge: histamine is required for IL-4-driven eosinophilic allergic responses.
Swartzendruber JA
, Byrne AJ, Bryce PJ.  J Immunol. 2012 Jan 15;188(2):536-40

The developmental regulator protein Gon4l associates with protein YY1, co-repressor Sin3a, and histone deacetylase 1 and mediates transcriptional repression.
Lu P, Hankel IL, Hostager BS, Swartzendruber JA, Friedman AD, Brenton JL, Rothman PB, Colgan JD. J Biol Chem. 2011 May 20;286(20):18311-9.

Publications from the Knight lab relevant to project:

Protection from intestinal inflammation by bacterial exopolysaccharides.
Jones SE, Paynich ML, Kearns DB, Knight KL. J Immunol. 2014 May 15;192(10):4813-20.

Bacillus subtilis-mediated protection from Citrobacter rodentium-associated enteric disease requires espH and functional flagella.
Jones SE, Knight KL. Infect Immun. 2012 Feb;80(2):710-9