P Sansonetti

..These data can now be used to understand the mechanisms of mucosal protection against bacillary dysentery...

..This review attempts to delineate the (sometimes thin) border between these two situations that are at the heart of understanding gut homeostasis and its possible rupture...

..Subsequent apoptotic killing of macrophages in a caspase 1-dependent process causes the release of IL-1beta and IL-18, which accounts for the initial steps of inflammation...

..Finally, a variety of strategies also exist to deal with other components of the epithelial barrier, such as macrophages. Pro-phagocytic, anti-phagocytic, and pro-apoptotic processes appear to be of particular importance...

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..It is becoming clear that the host immune system must reach a delicate balance between destroying dangerous bacterial pathogens while preserving the beneficial gut microbiota...

..Once they are intracellular, bacteria multiply within the cytoplasm and move from cell to cell by an actin-dependent process...

..Bacteria then lyse the two membranes, reach the cytoplasmic compartment again, and resume actin-driven movement...

..By mediating eradication of bacteria at their epithelial entry site, although at the cost of severe epithelial destruction, IL-8 therefore appears to be a key chemokine in the control of bacterial translocation...

..This review discusses the mechanisms for establishing and controlling the 'dialogue' between unresponsiveness and initiation of active immune defences in the gut. Si vis pacem, para bellum. (If you wish for peace, prepare for war.)...

..A growing number of non-Toll-like innate immune receptors is recognized as part of this surveillance network...

..These experiments demonstrate that various remodeling patterns may occur in Peyer's patches in response to bacterial pathogens, depending on the virulence phenotype expressed by the pathogenic strain...

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..We have taken enteroinvasive micro-organisms such as Yersinia, Shigella and Salmonella as a paradigm of the significance of phagocytosis/antiphagocytosis in the development of an infection and on the elicitation of the host response...

..Moreover, in vitro blockade of CD14 did not impede bactericidal activity. Thus, anti-CD14 treatment interfered with host defense mechanisms involved with removal/eradication of Shigella...

..We propose that IpaB and IpaD, by interacting in the secretion apparatus, modulate secretion...

..Additionally, the characterization of Nod2 as the first pathogen-recognition molecule that detects MDP will help to unravel the well known biological activities of this immunomodulatory compound...

..The IpaB-CD44 interaction appears to be required for Shigella invasion by initiating the early steps of the entry process...

..Moreover, we show that in epithelial cells (which represent the first line of defense against invasive pathogens), Nod1is indispensable for intracellular Gram-negative bacterial sensing...

..In contrast, higher quantities of TNF-alpha were observed in the CD14-blocked group. To conclude, anti-CD14 treatment had a detrimental effect on the capacity of Shigella-infected animals to clear the infection...

..Secreton morphology did not change upon activation of secretion. In mutants of some genes encoding the secretion machinery the organelle was absent, whereas ipaB and ipaC mutants displayed normal secretons...

..casei treatment. Thus, L. casei has developed a sophisticated means to maintain intestinal homeostasis through a process that involves manipulation of the ubiquitin/proteasome pathway upstream of I-kappaBalpha...

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..Our data provide evidence that membrane association is linked to Nod1 function and, in view of recent findings on Nod2, that this may be a common feature of NLR family members...

..This finding indicates that OspG negatively controls the host innate response induced by S. flexneri upon invasion of the epithelium...

..We also present evidence that at least one ipaH gene that is carried by the chromosome is controlled by MxiE and IpgC...

..As MxiH was present in NCs in large molar excess, we propose that it is the major needle component. MxiI may cap at the external needle tip...

..This is a major step forward in the development of a murine model of bacillary dysentery...

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..This synthetic carbohydrate-based conjugate may be a candidate for a SF2a vaccine...

..The homology between TLRs and the Toll system in Drosophila suggests that conserved defense mechanisms are likely to be shared by diverse organisms...

..Thus, S. flexneri has developed a dedicated strategy to weaken the innate immunity to manage its survival and colonization ability in the intestine...

..flexneri infection through amplification of an inflammatory response. This cellular lymphocyte redundancy assures IFN-gamma production, which is central to innate immunity against Shigella infection...

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..A pentadecasaccharide representing three biological repeating units was identified as a potential candidate for further development of a chemically defined glycoconjugate vaccine against S. flexneri 2a infection...

..MRI thus represents a powerful technique to study in vivo the interactions between a pathogen and its host in real time...

..These results indicate that the IpaC effector domain determines Src-dependent actin polymerization and ruffle formation during bacterial invasion...

..S. flexneri has thus evolved the capacity to precisely modulate host cell epigenetic 'information' as a strategy for repressing innate immunity...

..These results suggest that IpaA regulates actin polymerisation/depolymerisation at sites of Shigella invasion by modulating the barbed end capping activity of vinculin...

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..The escape strategies, the possible direct effect of Shigella 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...

..In a recent paper, Foster et al. (2007) demonstrate that this subtle balance is established and imprinted via epigenetic regulation...

..These data provide the molecular basis for a new mechanism employed by a pathogenic bacterium to promote membrane ruffling at the entry site...

..Therefore, binding of IgA(d/p) to SC during the course of SIgA-mediated mucosal response constitutes a crucial step in achieving efficient protection of the epithelial barrier by immune exclusion...

..Thus, intracellular neutralization by dIgA limits the acute local inflammation induced by proinflammatory pathogen-associated molecular patterns such as LPS...

..By defining the PG structural requirements for Nod1 and Nod2 sensing, this study reveals how PG processing and modifications, either by host or bacterial enzymes, may affect innate immune responses...

..Together, studies on Nod2 (Card15) provide a conceptual link between inflammatory disorders, such as Crohn's disease and Blau syndrome, and bacterial sensing...

..The mechanisms underlying bacterial entry, phagosome maturation, and dissemination reveal common strategies as well as unique tactics evolved by individual species to establish infection...

..These results point at a major role for a Crk-cortactin complex in actin polymerization downstream of tyrosine kinase signaling...

..pylori than were wild-type mice. We propose that sensing of H. pylori by Nod1 represents a model for host recognition of noninvasive pathogens...

..Homotypic interactions were identified with the baits IpaA, IpaB and IpaC. Interactions between effectors and components of the TTS machinery were also selected that might give insights into regulation of the TTS process...

..We propose that IpgC, which is not secreted and thus acts as a molecular chaperone, serves as a receptor that prevents premature oligomerization of IpaB and IpaC within the cytoplasm of Shigella cells...

..More basic research is also required to improve what we can still consider as first-generation vaccines, and to explore possible new paradigms including the search for cross-protective antigens...

..This study thereby identifies Nod1 as the long sought after sensor of TCT in mammals...

..These results indicate that cytoplasmic polar localization directs secretion of IpaC at the pole of Shigella, and may represent a mandatory step for T3S...

..This study assigns a function for IpaH family members as E3 ubiquitin ligases...

..8, 26 and 8.5. Serum antibody responses were seen in three subjects. SC599 appears immunogenic with maximum tolerated dose greater than 10(8)CFU...

..Dramatic increase in IL-8 gene transcription points to this chemokine as the major molecule orchestrating mucosal inflammation in shigellosis...

..These reveal that the two sensing-systems are non-redundant in bacterial recognition and that their cross-talk plays an important role in immunological homeostasis...

..In addition, the number and localization of uroids were modified. These results suggest a role for EhRacG in amoebic morphogenesis and cytokinesis...

..Furthermore, the inhibition of the expression of SOCS1 by IL-10 in the absence of adherence, may explain its priming effects on a subsequent LPS stimulation that we previously described...

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..Because mice are naturally resistant to shigellosis, there is no mouse model that mimics human disease. We explore the susceptibility of intestinal flora-depleted mice to shigellosis after intragastric infection with Shigella strains...

..Thus, S. flexneri parasitism is shedding light onto a new mechanism of PI 3-kinase/Akt activation via PtdIns5P production that plays an important role in host cell responses such as survival...

..typhimurium-induced proinflammatory responses through basolateral TLR5 and is consistent with the emerging model of S. typhimurium flagellin-induced inflammation...

..The rapid death of DC during the early stages of shigellosis is likely to have adverse consequences for generation of adaptive immunity...

..Together, our results identified a cross-talk between the Nod1 and Nod2 pathways and suggested that down-regulation of Nod1/M-Tri(DAP) pathway may be associated with Crohn disease...

..Thus, the reduced virulence of KFV101 makes it a prototype for multi-toxin deleted vaccine strains that could be used for protection against V. cholerae without the adverse effects of the accessory cholera toxins...

..This delayed apoptosis may have important effects on the ordered initiation of the innate immune response, leading to the excessive inflammatory response characteristic of shigellosis...

..In the guinea pig, administration of Shigella by i.r. route induces acute inflammation, making this animal model useful for assessing the protective efficacy of Shigella vaccine candidates...

..Taken together, our results indicate that NOD2 may represent a new therapeutic target in liver diseases...

..dysenteriae type 1 infection was associated with a significant up-regulation of Fas/Fas-L and perforin and granzyme A expression and a down-regulation of Bcl-2 and IL-2, which promote cell survival...