Montana INBRE (IDeA Networks of Biomedical Research Excellence)

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The Montana INBRE Program (IDeA Networks of Biomedical Research Excellence) is a five-year award (2009-2014) by the National Institute of General Medical Sciences (NIGMS) division of the National Institutes of Health (NIH) that builds on the previous successes of the first five-year MT INBRE program (2004-2009) and the three-year BRIN (Biomedical Research Infrastructure Networks) program (2001-2004) awarded to Montana State University. Montana INBRE continues to focus on increasing the biomedical research capacity of Montana by building research infrastructure, supporting faculty and student research, and fostering a state-wide collaborative network. The pathogenesis of infectious disease and health issues related to the environment are two of Montana INBRE’s research foci, areas in which the state is strategically positioned to excel. In addition, MT INBRE is expanding its research into the field of health disparities, an area of great relevance to the state. INBRE positions Montana as a leader in biomedical research and significantly increases education, research, and, ultimately, employment opportunities in the state.

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    Virus-like Particle-Induced Protection against MRSA Pneumonia Is Dependent on IL-13 and Enhancement of Phagocyte Function
    (2012-07) Rynda-Apple, Agnieszka; Dobrinen, Erin; McAlpine, Mark; Read, Amanda; Harmsen, Ann L.; Richert, Laura E.; Calverley, Matthew; Pallister, Kyler; Voyich, Jovanka M.; Wiley, James A.; Johnson, Ben; Young, Mark J.; Douglas, Trevor; Harmsen, Allen G.
    The importance of the priming of the lung environment by past infections is being increasingly recognized. Exposure to any given antigen can either improve or worsen the outcome of subsequent lung infections, depending on the immunological history of the host. Thus, an ability to impart transient alterations in the lung environment in anticipation of future insult could provide an important novel therapy for emerging infectious diseases. In this study, we show that nasal administration of virus-like particles (VLPs) before, or immediately after, lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA) of mice i) ensures complete recovery from lung infection and near absolute clearance of bacteria within 12 hours of challenge, ii) reduces host response-induced lung tissue damage, iii) promotes recruitment and efficient bacterial clearance by neutrophils and CD11c+ cells, and iv) protects macrophages from MRSA-induced necrosis. VLP-mediated protection against MRSA relied on innate immunity. Complete recovery occurred in VLP-dosed mice with severe combined immunodeficiency, but not in wild-type mice depleted of either Ly6G+ or CD11c+ cells. Early IL-13 production associated with VLP-induced CD11c+ cells was essential for VLP-induced protection. These results indicate that VLP-induced alteration of the lung environment protects the host from lethal MRSA pneumonia by enhancing phagocyte recruitment and killing and by reducing inflammation-induced tissue damage via IL-13–dependent mechanisms.
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