200 production may be exploited by these pathogens to promote their colonization by suppressing the growth of competitors. Other metal ions such as zinc and manganese are also essential micronutrients for bacteria. The antimicrobial peptide calprotectin, which is present in neutrophil granules, chelates zinc, and manganese, is involved in host defense against bacterial infections [93]. Expression of the S100A8 and S100A9 subunits of calprotectin is induced in the mucosa in response to IL-17 and IL-22 stimulation [34, 94]. The role that this and other antimicrobial peptides play in host defense to pathogens remains to be established. Conclusions The function of the cytokines IL-17, IL-22, and IL-23 in response to gut pathogens is summarized in the model proposed in Fig. 1. Dendritic cells activated by pathogens secrete cytokines including IL-22 and IL-23 [34, 95]. Several innate-like and adaptive T cells harbor the IL-23 receptor and are activated by this cytokine to release IL-17 and IL-22 [11]. These cytokines stimulate epithelial cells to express CXC chemokines resulting in neutrophil recruit- ment to the site of infection. Neutrophils constitute part of the mucosal barrier against inflammatory diarrheal patho- gens by containing these infections to mucosal sites and preventing bacteremia [96]. IL-17 and IL-22 also induce the expression and secretion of antimicrobial peptides including lipocalin-2, Reg3γ, β- defensins, and calprotectin [34, 43, 49, 58]. Some of these antimicrobial peptides may control dissemination from the mucosa, as in the case of Reg3γ during C. rodentium infection [34], while others such as lipocalin-2 suppress the growth of commensal microbiota and consequently pro- mote the growth of resistant pathogens [49]. Pathogens which have adapted to this hostile environment have acquired a range of virulence factors that provide access to nutrients in the inflamed gut, including glycoproteins in the mucus layer and metal ions. Pathogens have thus evolved to take advantage of various aspects of the mucosal response to gain an edge over the resident microbiota in colonizing the inflamed gut. Even though the enhancement of pathogen colonization is a “side effect” of IL-17 and IL-22 mediated responses, resolution of diarrhea typically occurs within a few days of its onset. In contrast, defects in Th17-mediated responses like those observed in HIV patients result in increased dissemination of both pathogens and the microbiota, culminating in bacteremia with a high mortality rate [97, 98]. So while Th17 responses appear to be detrimental by promoting pathogen colonization of the mucosa, in the end it is the resulting decrease in bacterial dissemination from the mucosa that protects the host. J Clin Immunol (2010) 30:196–203 Acknowledgments Work in the laboratory of MR is supported by Public Health Service Grant AI083619 and the IDSA ERF/NIFID Astellas Young Investigator Award. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which per- mits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. References 1. Bearman GM, Wenzel RP. Bacteremias: a leading cause of death. Arch Med Res. 2005;36:646–59. 2. McBean M, Rajamani S. Increasing rates of hospitalization due to septicemia in the US elderly population, 1986–1997. J Infect Dis. 2001;183:596–603. 3. Duerkop BA, Vaishnava S, Hooper LV. Immune responses to the microbiota at the intestinal mucosal surface. Immunity. 2009;31:368– 76. 4. Umesaki Y, Setoyama H, Matsumoto S, Imaoka A, Itoh K. Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system. Infect Immun. 1999;67:3504–11. 5. Aranda-Michel J, Giannella RA. Acute diarrhea: a practical review. Am J Med. 1999;106:670–6. 6. Mundy R, MacDonald TT, Dougan G, Frankel G, Wiles S. Citrobacter rodentium of mice and man. Cell Microbiol. 2005;7:1697–706. 7. Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev 22:240–73, Table of Contents 2009. 8. van Wijk F, Cheroutre H. Intestinal T cells: facing the mucosal immune dilemma with synergy and diversity. Semin Immunol. 2009;21:130–8. 9. Inagaki-Ohara K, Dewi FN, Hisaeda H, Smith AL, Jimi F, Miyahira M, et al. Intestinal intraepithelial lymphocytes sustain the epithelial barrier function against Eimeria vermiformis infection. Infect Immun. 2006;74:5292–301. 10. Klein JR. T-cell activation in the curious world of the intestinal intraepithelial lymphocyte. Immunol Res. 2004;30:327–37. 11. Agace WW. T-cell recruitment to the intestinal mucosa. Trends Immunol. 2008;29:514–22. 12. Zeitz M, Ullrich R, Schneider T, Kewenig S, Hohloch K, Riecken EO. HIV/SIV enteropathy. Ann N Y Acad Sci. 1998;859:139–48. 13. Guadalupe M, Reay E, Sankaran S, Prindiville T, Flamm J, McNeil A, et al. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol. 2003;77:11708–17. 14. Smit-McBride Z, Mattapallil JJ, McChesney M, Ferrick D, Dandekar S. Gastrointestinal T lymphocytes retain high potential for cytokine responses but have severe CD4(+) T-cell depletion at all stages of simian immunodeficiency virus infection compared to peripheral lymphocytes. J Virol. 1998;72:6646–56. 15. Gamberg J, Barrett L, Bowmer MI, Howley C, Grant M. Factors related to loss of HIV-specific cytotoxic T lymphocyte activity. AIDS. 2004;18:597–604. 16. Glaser JB, Morton-Kute L, Berger SR, Weber J, Siegal FP, Lopez C, et al. Recurrent Salmonella typhimurium bacteremia associated with the acquired immunodeficiency syndrome. Ann Intern Med. 1985;102:189–93. 17. Gordon MA. Salmonella infections in immunocompromised adults. J Infect. 2008;56:413–22. 18. Tee W, Mijch A. Campylobacter jejuni bacteremia in human immunodeficiency virus (HIV)-infected and non-HIV-infected