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

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI049316-10
Application #
8197276
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Rothermel, Annette L
Project Start
2001-04-01
Project End
2013-11-30
Budget Start
2011-12-01
Budget End
2013-11-30
Support Year
10
Fiscal Year
2012
Total Cost
$367,538
Indirect Cost
$122,513
Name
University of Maryland Baltimore
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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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
Yang, Zhonghan; Sun, Rex; Grinchuk, Viktoriya et al. (2013) IL-33-induced alterations in murine intestinal function and cytokine responses are MyD88, STAT6, and IL-13 dependent. Am J Physiol Gastrointest Liver Physiol 304:G381-9
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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