Project description:Leber2015 - Mucosal immunity and gut
microbiome interaction during C. difficile infection
This model is described in the article:
Systems Modeling of
Interactions between Mucosal Immunity and the Gut Microbiome
during Clostridium difficile Infection.
Leber A, Viladomiu M, Hontecillas R,
Abedi V, Philipson C, Hoops S, Howard B, Bassaganya-Riera
J.
PLoS ONE 2015; 10(7): e0134849
Abstract:
Clostridium difficile infections are associated with the use
of broad-spectrum antibiotics and result in an exuberant
inflammatory response, leading to nosocomial diarrhea, colitis
and even death. To better understand the dynamics of mucosal
immunity during C. difficile infection from initiation through
expansion to resolution, we built a computational model of the
mucosal immune response to the bacterium. The model was
calibrated using data from a mouse model of C. difficile
infection. The model demonstrates a crucial role of T helper 17
(Th17) effector responses in the colonic lamina propria and
luminal commensal bacteria populations in the clearance of C.
difficile and colonic pathology, whereas regulatory T (Treg)
cells responses are associated with the recovery phase. In
addition, the production of anti-microbial peptides by inflamed
epithelial cells and activated neutrophils in response to C.
difficile infection inhibit the re-growth of beneficial
commensal bacterial species. Computational simulations suggest
that the removal of neutrophil and epithelial cell derived
anti-microbial inhibitions, separately and together, on
commensal bacterial regrowth promote recovery and minimize
colonic inflammatory pathology. Simulation results predict a
decrease in colonic inflammatory markers, such as neutrophilic
influx and Th17 cells in the colonic lamina propria, and length
of infection with accelerated commensal bacteria re-growth
through altered anti-microbial inhibition. Computational
modeling provides novel insights on the therapeutic value of
repopulating the colonic microbiome and inducing regulatory
mucosal immune responses during C. difficile infection. Thus,
modeling mucosal immunity-gut microbiota interactions has the
potential to guide the development of targeted fecal
transplantation therapies in the context of precision medicine
interventions.
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Project description:Avian infectious bronchitis virus (IBV) infection is a major chicken viral respiratory disease that causes significant economic losses to the poultry industry worldwide. The local mucosal immune response plays a vital role against the infection of this respiratory virus. Previous studies have indicated that a variety of innate immunity and a Th1 based adaptive immunity are activated in the host’s early defense (3 days post inoculation, dpi) against IBV invasion and they are responsible for the rapid clearance of virus from the local infection. In the present study, we propose to use IBV as a model system to uncover the molecular mechanism of mucosal immunity development by characterizing the kinetics of the local gene transcription profiles in trachea tissues after administration with an attenuated IBV strain (IBV-Mass). More specifically, immune-related gene transcription profiles in trachea at 1, 3, 5, 8, 12 and 21 days after the primary immunization and at 1 and 2 days after a second immunization were monitored using chicken 13K cDNA Microarray. Keywords: time course, cDNA 13k chicken array from FHCRC, IBV-chicken model
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