an immune-mediated protection against colitis along with improved colonic function. Our preliminary data led us to focus our efforts in this proposal on the specific mechanisms by which enteric infection alters gut function. The proposed studies contain 3 specific aims that are designed to test the following two central hypotheses: 1) infection-induced development and duration of changes in gut function are mediated by direct effects of cytokines on structural cells and on the interaction between structural and immune cells (Specific Aims 1 and 2);and 2) members of the IL-17 cytokine family are important in regulation of the functional effects associated with the Th1 or Th2 profiles (Specific Aim 3). The proposed approach will use mice infected with natural rodent pathogens, in vivo and in vitro studies of mucosal and smooth muscle function, primary cultures of immune cells, and molecular and immunohistochemical analyses. These studies will help us to understand how the host exploits physiological mechanisms in its defense against pathogens that allow for the stereotypic functional responses that promote expulsion. The impact of these studies is evident in that dysregulation of these functional changes significantly impairs host resistance and the maintenance of adequate barrier function and nutrient absorption. These studies also will provide insight on the mechanisms involved in the ability of nematode infection to protect against the development of autoimmune diseases, many of which are characterized by impaired intestinal barrier function. Project Description Page 6

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Rothermel, Annette L
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University of Maryland Baltimore
Internal Medicine/Medicine
Schools of Medicine
United States
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McLean, Leon P; Smith, Allen; Cheung, Lumei et al. (2015) Type 3 Muscarinic Receptors Contribute to Clearance of Citrobacter rodentium. Inflamm Bowel Dis 21:1860-71
Wang, An-Jiang; Yang, Zhonghan; Grinchuk, Viktoriya et al. (2015) IL-25 or IL-17E Protects against High-Fat Diet-Induced Hepatic Steatosis in Mice Dependent upon IL-13 Activation of STAT6. J Immunol 195:4771-80
Fernández-Blanco, Joan Antoni; Estévez, Javier; Shea-Donohue, Terez et al. (2015) Changes in Epithelial Barrier Function in Response to Parasitic Infection: Implications for IBD Pathogenesis. J Crohns Colitis 9:463-76
Shea-Donohue, Terez; Sun, Rex; Bohl, Jennifer A et al. (2015) Enteric nematodes and the path to up-regulation of type 2 cytokines IL-4 and IL-13. Cytokine 75:62-7
Fricke, W Florian; Song, Yang; Wang, An-Jiang et al. (2015) Type 2 immunity-dependent reduction of segmented filamentous bacteria in mice infected with the helminthic parasite Nippostrongylus brasiliensis. Microbiome 3:40
Shea-Donohue, Terez; Zhao, Aiping; Antalis, Toni M (2014) SerpinB2 mediated regulation of macrophage function during enteric infection. Gut Microbes 5:254-8
Notari, Luigi; Riera, Diana C; Sun, Rex et al. (2014) Role of macrophages in the altered epithelial function during a type 2 immune response induced by enteric nematode infection. PLoS One 9:e84763
McLean, Leon P; Cross, Raymond K; Shea-Donohue, Terez (2013) Combined blockade of IL-17A and IL-17F may prevent the development of experimental colitis. Immunotherapy 5:923-5
Yang, Zhonghan; Grinchuk, Viktoriya; Urban Jr, Joseph F et al. (2013) Macrophages as IL-25/IL-33-responsive cells play an important role in the induction of type 2 immunity. PLoS One 8:e59441
Zhao, Aiping; Yang, Zhonghan; Sun, Rex et al. (2013) SerpinB2 is critical to Th2 immunity against enteric nematode infection. J Immunol 190:5779-87

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