J Clin Immunol (2010) 30:196–203 DOI 10.1007/s10875-010-9368-7 Th17 Cytokines and the Gut Mucosal Barrier Christoph Blaschitz & Manuela Raffatellu Received: 29 December 2009 / Accepted: 7 January 2010 / Published online: 2 February 2010 # The Author(s) 2010. This article is published with open access at Springerlink.com Abstract Local immune responses serve to contain infections by pathogens to the gut while preventing pathogen dissemination to systemic sites. Several sub- sets of T cells in the gut (T-helper 17 cells, γδ T cells, natural killer (NK), and NK-T cells) contribute to the mucosal response to pathogens by secreting a subset of cytokines including interleukin (IL)-17A, IL-17F, IL-22, and IL-26. These cytokines induce the secretion of chemokines and antimicrobial proteins, thereby orches- trating the mucosal barrier against gastrointestinal pathogens. While the mucosal barrier prevents bacterial dissemination from the gut, it also promotes coloniza- tion by pathogens that are resistant to some of the inducible antimicrobial responses. In this review, we describe the contribution of Th17 cytokines to the gut mucosal barrier during bacterial infections. Keywords IL-17 . IL-22 . gut inflammation . Th17 Intestinal Pathogens and the Gut Mucosal Barrier In normal individuals, the gut mucosa constitutes a barrier against the systemic spread of both pathogenic microorgan- isms and the resident intestinal microbiota. Once this barrier C. Blaschitz : M. Raffatellu (*) Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, CA 92697, USA e-mail: manuelar@uci.edu C. Blaschitz : M. Raffatellu Institute of Immunology, University of California Irvine, Irvine, CA 92697, USA has been breached, dissemination of microbes from the gut can result in a systemic disease known generally as sepsis. With regards to bacteria, the frequency of bacteremia (bacterial sepsis) is higher in patients with altered mucosal immunity (such as children and the elderly) as well as in patients affected by immunodeficiency, implicating the mucosal barrier as an important line of defense against bacterial dissemination [1, 2]. Similarly, increased perme- ability of the mucosal barrier with concomitant bacterial translocation has been reported in Crohn’s disease [2]. A portion of the gut mucosal barrier function is orchestrated by the intestinal microbiota that coexist with the host in a mutually beneficial symbiosis [3]. These functions include inducing secretory IgA production and intraepithelial lymphocyte recruitment as well as providing a physical blockade to pathogen colonization [4]. At least one of these mucosal defenses or others to be detailed below must be circumvented or endogenously fail for pathogens or the resident microbiota to disseminate beyond the gut mucosa. Some intestinal pathogens including nontyphoidal Salmo- nella (including Salmonella typhimurium), Campylobacter, and Shigella cause inflammatory diarrhea and are character- ized by their ability to invade the intestinal mucosa. In stark contrast to these organisms, the closely related pathogens enterohemorrhagic Escherichia coli (EHEC) and enteropatho- genic E. coli (EPEC), among others, cause secretory diarrhea and are noninvasive [5]. With regards to the latter group, these strains of E. coli belong to the class of organisms known as attaching–effacing (AE) bacteria because they form charac- teristic AE lesions as a result of their intimate adhesion with the intestinal mucosa. As both EHEC and EPEC are poorly pathogenic in mice, Citrobacter rodentium, a natural mouse pathogen related to E. coli which also causes AE lesion formation, has been widely used as an experimental model for AE pathogens and will thus be included in this discussion [6].