Hospital acquired pneumonia costs up to $2-billion per year in the United States and inexpensive therapies which reduce these septic complications could greatly impact healthcare costs. Enteral feeding significantly reduces infectious complications compared with intravenous (IV-TPN) feeding or starvation by 60-70% in trauma patients. Our experimental and clinical work implicates previously unrecognized defects in mucosal immunity which occur when the intestinal tract is not stimulated with enteral feeding or by administration of surrogates of enteral feeding (glutamine or bombesin). The principle immunological defense of mucosal surfaces is secretory IgA produced by mucosal-associated lymphoid tissue (MALT). The principle anatomic site for immunologic sensitization occurs in Peyer's patches in the small intestine with subsequent delivery of sensitized cells to the respiratory and Gl tracts. IV-TPN reduces expression of an important adhesion molecule MAdCAM-1 which directs unsensitized immunocytes via their integrins into Peyer's patches where they are subsequently sensitized. The integrins change with sensitization and the cells are directed to both intestinal and extra-intestinal sites where they produce IgA against those antigens. IV-TPN reduces T and B cells within these sites and significantly reduces IgA levels. IgA normally binds to bacteria, preventing their attachment and their ability to infect. Our extensive animal work demonstrates that enteral feeding maintains normal MALT through multiple mechanisms including preservation of cytokines responsible for adhesion molecule expression and IgA production. In addition, we have shown reduced transport of IgA across the secretory epithelium. The current proposal focuses on other aspects of cell homing and IgA delivery including a) the expression of lymphotoxin beta receptor which controls the production of chemokines, adhesion molecules and cytokines important in mucosal immunity b) the effect of route and type of nutrition on levels of chemokines which induce site specific migration of cells containing receptors to these chemokines within the MALT and c) after better defining specific changes in cell profiles within MALT sites in response to route and type of nutrition, glutamine, or bombesin, we will track homing of subpopulations of MALT cells in vivo using inbred mice. We will test the ability of these cells to reverse a defect in production of IgA that occurs after injury. These experiments are designed to confirm the critical need for enteral stimulation to maximize function of mucosal immunity and further define the diffuse effects that route and type of nutrition generates throughout the mucosal immune system.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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Somers, Scott D
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University of Wisconsin Madison
Schools of Medicine
United States
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Pierre, Joseph F; Busch, Rebecca A; Kudsk, Kenneth A (2016) The gastrointestinal immune system: Implications for the surgical patient. Curr Probl Surg 53:11-47
Collaud, Stéphane; Fadel, Elie; Schirren, Joachim et al. (2015) En Bloc Resection of Pulmonary Sulcus Non-small Cell Lung Cancer Invading the Spine: A Systematic Literature Review and Pooled Data Analysis. Ann Surg 262:184-8
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