ARS | Publication request: Enteric pathogens and gut function: role of cytokines and STATs

Submitted to: Gut Microbes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 12, 2010
Publication Date: September 1, 2010
Citation: Shea-Donohue, T., Fasano, A., Smith, A.D., Zhao, A. 2010. Enteric pathogens and gut function: role of cytokines and STATs. Gut Microbes. 1(5):316-324.

Interpretive Summary: The lining of the intestine is considered to be the initial site of interaction with organisms (both those which may assist in health and those which are pathogenic), and it contains the largest aggregation of immune cells in the body. Therefore, it is the first line of defense against infection. In response to the invasion of various pathogens, cells of the immune system change into different types of cells which make proteins called cytokines that help resist infection. Cytokines bind to both immune and non-immune cells leading to activation of specific pathways that influence gut function by increasing the expression of specific genes which make specific molecules that assist in combating the invading organism. This review considers the roles of cytokines and internal regulatory molecules called STATs that affect the response to pathogens and induce changes in gut function. The focus is on STAT4 and STAT6 because of their central role in the development of two major cytokine pathways called Th1 (which combats pathogens inside cells) and Th2 (which removes pathogens and allergens when located outside cells). This information will be of interest to scientists studying the role of cytokines in immune response to both allergens and pathogens.

Technical Abstract: The gut harbors the largest immune system in the body. The mucosa is considered to be the initial site of interaction with commensal and pathogenic organisms; therefore, it is the first line of defense against pathogens. In response to the invasion of various pathogens, naïve CD4+ cells differentiate into subsets of T helper (Th) cells that are characterized by different cytokine profiles. Cytokines bind to cell surface receptors on both immune and non-immune cells leading to activation of the JAK-STAT signaling pathway and influence gut function by up-regulating the expression of specific target genes. This review considers the roles of cytokines and receptor-mediated activation of STATs on pathogen-induced changes in gut function. The focus on STAT4 and STAT6 is because of their requirement for the full development of Th1 and Th2 cytokine profiles.