innate immune response to Salmonella. The recent discovery of NLRs and the inflammasome has significantly expanded the repertoire of possible innate immune detection mechanisms, yet the function of most known NLRs remains undiscovered. In addition, it has become clear that different cell types express a distinct set of PRRs and might trigger a different inflammatory program in response to pathogen infection. Finally, future studies will also need to address how the different innate immune responses shape adaptive immune responses and how this influences Salmonella pathogenesis. References 1. Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell 2010; 140:771-6; PMID:20303867; http://dx.doi.org/10.1016/j.cell.2010.03.006 2. Vance RE, Isberg RR, Portnoy DA. Patterns of pathogenesis: discrimination of pathogenic and non- pathogenic microbes by the innate immune system. Cell Host Microbe 2009; 6:10-21; PMID:19616762; http://dx.doi.org/10.1016/j.chom.2009.06.007 3. Saleh M, Trinchieri G. Innate immune mechanisms of colitis and colitis-associated colorectal cancer. Nat Rev Immunol 2011; 11:9-20; PMID:21151034; http://dx. doi.org/10.1038/nri2891 4. Monack DM, Mueller A, Falkow S. Persistent bacterial infections: the interface of the pathogen and the host immune system. Nat Rev Microbiol 2004; 2:747-65; PMID:15372085; http://dx.doi.org/10.1038/nrmicro955 5. Que JU, Hentges DJ. Effect of streptomycin admini- stration on colonization resistance to Salmonella typhi- murium in mice. Infect Immun 1985; 48:169-74; PMID:3884509 6. Winter SE, Thiennimitr © P, Winter 2012 MG, Butler BP, Huseby DL, Crawford RW, et al. Gut inflammation provides a respiratory electron acceptor for Salmonella. Nature 2010; 467:426-9; PMID:20864996; http://dx. doi.org/10.1038/nature09415 7. Haraga A, Ohlson MB, Miller SI. Salmonellae inter- play with host cells. Nat Rev Microbiol 2008; 6: nrmicro1788 Do 53-66; PMID:18026123; http://dx.doi.org/10.1038/ 8. Wagner C, Hensel M. Adhesive mechanisms of Salmonella enterica. Adv Exp Med Biol 2011; 715:17-34; PMID:21557055; http://dx.doi.org/10. 1007/978-94-007-0940-9_2 9. Jones BD, Ghori N, Falkow S. Salmonella typhimur- ium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer’s patches. J Exp Med 1994; 180:15-23; PMID: 8006579; http://dx.doi.org/10.1084/jem.180.1.15 10. Francis CL, Starnbach MN, Falkow S. Morphological and cytoskeletal changes in epithelial cells occur immediately upon interaction with Salmonella typhi- murium grown under low-oxygen conditions. Mol Microbiol 1992; 6:3077-87; PMID:1360615; http:// dx.doi.org/10.1111/j.1365-2958.1992.tb01765.x 11. Jepson MA, Collares-Buzato CB, Clark MA, Hirst BH, Simmons NL. Rapid disruption of epithelial barrier function by Salmonella typhimurium is associated with structural modification of intercellular junctions. Infect Immun 1995; 63:356-9; PMID:7806378 12. Vazquez-Torres A, Jones-Carson J, Bäumler AJ, Falkow S, Valdivia R, Brown W, et al. Extraintestinal dissem- ination of Salmonella by CD18-expressing phagocytes. Nature 1999; 401:804-8; PMID:10548107; http://dx. doi.org/10.1038/44593 13. Niess JH, Brand S, Gu X, Landsman L, Jung S, McCormick BA, et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 2005; 307:254-8; PMID:15653504; http://dx. doi.org/10.1126/science.1102901 14. Ohteki T, Suzue K, Maki C, Ota T, Koyasu S. Critical role of IL-15-IL-15R for antigen-presenting cell func- tions in the innate immune response. Nat Immunol 2001; 2:1138-43; PMID:11702064; http://dx.doi.org/ 10.1038/ni729 15. Bevins CL, Salzman NH. Paneth cells, antimicrobial 27. Miller SI, Kukral AM, Mekalanos JJ. A two-component peptides and maintenance of intestinal homeostasis. regulatory system (phoP phoQ) controls Salmonella Nat Rev Microbiol 2011; 9:356-68; PMID:21423246; typhimurium virulence. Proc Natl Acad Sci U S A http://dx.doi.org/10.1038/nrmicro2546 1989; 86:5054-8; PMID:2544889; http://dx.doi.org/ 16. Ouellette AJ. Paneth cell alpha-defensin synthesis and 10.1073/pnas.86.13.5054 function. Curr Top Microbiol Immunol 2006; 306:1- 28. Fischbach MA, Lin H, Zhou L, Yu Y, Abergel RJ, Liu 25; PMID:16909916; http://dx.doi.org/10.1007/3- DR, et al. The pathogen-associated iroA gene cluster 540-29916-5_1 mediates bacterial evasion of lipocalin 2. Proc Natl Acad 17. Godinez I, Raffatellu M, Chu H, Paixão TA, Haneda Sci U S A 2006; 103:16502-7; PMID:17060628; T, Santos RL, et al. Interleukin-23 orchestrates http://dx.doi.org/10.1073/pnas.0604636103 mucosal responses to Salmonella enterica serotype 29. Medzhitov R. Toll-like receptors and innate immunity. Typhimurium in the intestine. Infect Immun 2009; Nat Rev Immunol 2001; 1:135-45; PMID:11905821; 77:387-98; PMID:18955477; http://dx.doi.org/10. http://dx.doi.org/10.1038/35100529 1128/IAI.00933-08 30. Tükel C, Raffatellu M, Humphries AD, Wilson RP, 18. Brandl K, Plitas G, Mihu CN, Ubeda C, Jia T, Fleisher Andrews-Polymenis HL, Gull T, et al. CsgA is a M, et al. Vancomycin-resistant enterococci exploit pathogen-associated molecular pattern of Salmonella antibiotic-induced innate immune deficits. Nature enterica serotype Typhimurium that is recognized by 2008; 455:804-7; PMID:18724361; http://dx.doi.org/ Toll-like receptor 2. Mol Microbiol 2005; 58:289-304; 10.1038/nature07250 PMID:16164566; http://dx.doi.org/10.1111/j.1365- 19. Stelter C, Käppeli R, König C, Krah A, Hardt WD, 2958.2005.04825.x Stecher B, et al. Salmonella-induced mucosal lectin 31. Weiss DS, Raupach B, Takeda K, Akira S, Zychlinsky A. RegIIIβ kills competing gut microbiota. PLoS One Toll-like receptors are temporally involved in host defense. L10a.1371/njournadl.pone.e00207s49 Bios3c2.AirpaeiaN, Gnodec J, cLau eL,Siv.ick KE, McLaughlin LM, 2011; 6:e20749; PMID:21694778; http://dx.doi.org/ J Immunol 2004; 172:4463-9; PMID:15034062 20. Brandl K, Plitas G, Schnabl B, DeMatteo RP, Pamer Jones MB, et al. TLR signaling is required for EG. MyD88-mediated signals induce the bactericidal Salmonella typhimurium virulence. Cell 2011; 144: lectin RegIII gamma and protect mice against intestinal 675-88; PMID:21376231; http://dx.doi.org/10.1016/ Listeria monocytogenes infection. J Exp Med 2007; j.cell.2011.01.031 n10o84/jemt.20070d563 istributeJL..Cutting edge: bacterial flagellin activates basolat- 204:1891-900; PMID:17635956; http://dx.doi.org/10. 33. Gewirtz AT, Navas TA, Lyons S, Godowski PJ, Madara 21. Raffatellu M, George MD, Akiyama Y, Hornsby MJ, erally expressed TLR5 to induce epithelial proinflam- Nuccio SP, Paixao TA, et al. Lipocalin-2 resistance matory gene expression. J Immunol 2001; 167:1882-5; confers an advantage to Salmonella enterica sero- PMID:11489966 type Typhimurium for growth and survival in the 34. Kasper CA, Sorg I, Schmutz C, Tschon T, Wischnewski inflamed intestine. Cell Host Microbe 2009; 5:476-86; H, Kim ML, et al. Cell-cell propagation of NF-kB PMID:19454351; http://dx.doi.org/10.1016/j.chom. transcription factor and MAP kinase activation amplifies 2009.03.011 innate immunity against bacterial infection. Immunity 22. Raffatellu M, Santos RL, Verhoeven DE, George MD, 2010; 33:804-16; PMID:21093316; http://dx.doi.org/ Wilson RP, Winter SE, et al. Simian immunodeficiency 10.1016/j.immuni.2010.10.015 virus-induced mucosal interleukin-17 deficiency pro- 35. Broz P, Monack DM. Molecular mechanisms of motes Salmonella dissemination from the gut. Nat Med inflammasome activation during microbial infections. 2008; 14:421-8; PMID:18376406; http://dx.doi.org/ Immunol Rev 2011; 243:174-90; PMID:21884176; 10.1038/nm1743 http://dx.doi.org/10.1111/j.1600-065X.2011.01041.x 23. Raffatellu M, Santos RL, Chessa D, Wilson RP, Winter 36. Geddes K, Rubino S, Streutker C, Cho JH, Magalhaes SE, Rossetti CA, et al. The capsule encoding the viaB JG, Le Bourhis L, et al. Nod1 and Nod2 regulation of locus reduces interleukin-17 expression and mucosal inflammation in the Salmonella colitis model. Infect innate responses in the bovine intestinal mucosa during Immun 2010; 78:5107-15; PMID:20921147; http:// infection with Salmonella enterica serotype Typhi. dx.doi.org/10.1128/IAI.00759-10 Infect Immun 2007; 75:4342-50; PMID:17591794; 37. Martinon F, Burns K, Tschopp J. The inflammasome: a http://dx.doi.org/10.1128/IAI.01571-06 molecular platform triggering activation of inflammat- 24. Godinez I, Haneda T, Raffatellu M, George MD, ory caspases and processing of proIL-beta. Mol Cell Paixão TA, Rolán HG, et al. T cells help to amplify 2002; 10:417-26; PMID:12191486; http://dx.doi.org/ inflammatory responses induced by Salmonella enterica 10.1016/S1097-2765(02)00599-3 serotype Typhimurium in the intestinal mucosa. Infect 38. Broz P, von Moltke J, Jones JW, Vance RE, Monack Immun 2008; 76:2008-17; PMID:18347048; http:// DM. Differential requirement for Caspase-1 autopro- dx.doi.org/10.1128/IAI.01691-07 teolysis in pathogen-induced cell death and cytokine 25. Zheng Y, Valdez PA, Danilenko DM, Hu Y, Sa SM, processing. Cell Host Microbe 2010; 8:471-83; Gong Q, et al. Interleukin-22 mediates early host PMID:21147462; http://dx.doi.org/10.1016/j.chom. defense against attaching and effacing bacterial patho- 2010.11.007 gens. Nat Med 2008; 14:282-9; PMID:18264109; 39. Bergsbaken T, Fink SL, Cookson BT. Pyroptosis: host http://dx.doi.org/10.1038/nm1720 cell death and inflammation. Nat Rev Microbiol 26. Kato A, Groisman EA & Howard Hughes Medical 2009; 7:99-109; PMID:19148178; http://dx.doi.org/ Institute. The PhoQ/PhoP regulatory network of 10.1038/nrmicro2070 Salmonella enterica. Adv Exp Med Biol 2008; 631:7- 21; PMID:18792679; http://dx.doi.org/10.1007/978- 0-387-78885-2_2 www.landesbioscience.com Gut Microbes 69