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The so\u2010called invasive phenotype of\n                    <jats:italic>Shigella<\/jats:italic>\n                    is linked to expression of a type III secretory system (TTSS) injecting effector proteins into the epithelial cell membrane and cytoplasm, thereby inducing local but massive changes in the cell cytoskeleton that lead to bacterial internalization into non\u2010phagocytic intestinal epithelial cells. The invasive phenotype also accounts for the potent pro\u2010inflammatory capacity of the microorganism. Recent evidence indicates that a large part of the mucosal inflammation is initiated by intracellular sensing of bacterial peptidoglycan by cytosolic leucine\u2010rich receptors of the NOD family, particularly NOD1, in epithelial cells. This causes activation of the nuclear factor kappa B and c\u2010JunNH\n                    <jats:sub>2<\/jats:sub>\n                    \u2010terminal\u2010kinase pathways, with interleukin\u20108 appearing as a major chemokine mediating the inflammatory burst that is dominated by massive infiltration of the mucosa by polymorphonuclear leukocytes. Not unexpectedly, this inflammatory response, which is likely to be very harmful for the invading microbe, is regulated by the bacterium itself. A group of proteins encoded by\n                    <jats:italic>Shigella<\/jats:italic>\n                    , which are injected into target cells by the TTSS, has been recently recognized as a family of potent regulators of the innate immune response. These enzymes target key cellular functions that are essential in triggering the inflammatory response, and more generally defense responses of the intestinal mucosa. This review focuses on the mechanisms employed by\n                    <jats:italic>Shigella<\/jats:italic>\n                    to manipulate the host innate response in order to escape early bacterial killing, thus ensuring establishment of its infectious process. The escape strategies, the possible direct effect of\n                    <jats:italic>Shigella<\/jats:italic>\n                    on B and T lymphocytes, their impact on the development of adaptive immunity, and how they may help explain the limited protection induced by natural infection are discussed.\n                  <\/jats:p>","DOI":"10.1038\/sj.icb7100025","type":"journal-article","created":{"date-parts":[[2007,1,9]],"date-time":"2007-01-09T10:58:23Z","timestamp":1168340303000},"page":"119-129","source":"Crossref","is-referenced-by-count":210,"title":["<i>Shigella\u2019<\/i>\n                    s ways of manipulating the host intestinal innate and adaptive immune system: a tool box for survival?"],"prefix":"10.1111","volume":"85","author":[{"given":"Armelle","family":"Phalipon","sequence":"first","affiliation":[{"name":"Unit\u00e9 de Pathog\u00e9nie Microbienne Mol\u00e9culaire, INSERM U786  Institut Pasteur 25, Rue du Dr Roux Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe J","family":"Sansonetti","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Pathog\u00e9nie Microbienne Mol\u00e9culaire, INSERM U786  Institut Pasteur 25, Rue du Dr Roux Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,1,9]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/13.Supplement_4.S279"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/159.6.1126"},{"key":"e_1_2_11_3_1","first-page":"651","article-title":"Global burden of Shigella infections: implications for vaccine development and implementation of control strategies","volume":"77","author":"Kotloff KL","year":"1999","journal-title":"Bull WHO"},{"key":"e_1_2_11_4_1","first-page":"259","article-title":"Risk factors for mortality due to shigellosis: a case\u2013control study among severely\u2010malnourished children in Bangladesh","volume":"23","author":"Van den Broek JM","year":"2005","journal-title":"J Health PopulNutr"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268804002134"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-5-89"},{"key":"e_1_2_11_7_1","first-page":"339","article-title":"Prevalence of Shigella species and their antimicrobial resistance patterns in eastern Nepal","volume":"23","author":"Bhattacharya SKB","year":"2005","journal-title":"J Health Popul Nutr"},{"key":"e_1_2_11_8_1","first-page":"739","article-title":"Estimating the burden of shigellosis in Thailand: 36\u2010month population\u2010based surveillance study","volume":"83","author":"Chompook P","year":"2005","journal-title":"Bull WHO"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2005.72.851"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2005.01277.x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.MPG.0000153006.38363.7E"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268805004498"},{"key":"e_1_2_11_13_1","first-page":"184","article-title":"Frequency of isolation of Shigella serogroups\/serotypes and their antimicrobial susceptibility pattern in children from slum areas in Karachi","volume":"55","author":"Zafar A","year":"2005","journal-title":"J Pak Med Assoc"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2006.02.007"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.inf.0000198747.54971.b2"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(04)01143-0"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.3.1203-1205.2005"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00284-005-0140-9"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v23.i56.20"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.10.014"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.03.039"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/13.Supplement_4.S314"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/150.6.899"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1499"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2004.12.006"},{"key":"e_1_2_11_26_1","first-page":"503","article-title":"Experimental acute colitis in the rhesus monkey following peroral infection with Shigella flexneri. 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