Escherichia coli O157:H7 causes bloody diarrhea and potentially fatal systemic sequelae in humans. Cattle are most frequently identified as the primary source of infection, and E. coli O157:H7 generally colonizes the gastrointestinal tracts of cattle without causing disease. In this study, persistence and tropism were assessed for four different E. coli O157:H7 strains. Experimentally infected calves shed the organism for at least 14 days prior to necropsy. For the majority of these animals, as well as for a naturally colonized animal obtained from a commercial beef farm, the highest numbers of E. coli O157:H7 were found in the feces, with negative or significantly lower levels detected in lumen contents taken from the gastrointestinal tract. Detailed examination demonstrated that in these individuals the majority of tissue-associated bacteria were adherent to mucosal epithelium within a defined region extending up to 5 cm proximally from the recto-anal junction. The tissue targeted by E. coli O157:H7 was characterized by a high density of lymphoid follicles. Microcolonies of the bacterium were readily detected on the epithelium of this region by immunofluorescence microscopy. As a consequence of this specific distribution, E. coli O157:H7 was present predominately on the surface of the fecal stool. In contrast, other E. coli serotypes were present at consistent levels throughout the large intestine and were equally distributed in the stool. This is a novel tropism that may enhance dissemination both between animals and from animals to humans. The accessibility of this site may facilitate simple intervention strategies.Enterohemorrhagic Escherichia coli (EHEC) has emerged as an important cause of human intestinal disease in developed countries over the past 20 years. In addition to bloody diarrhea, intestinal infection can lead to potentially fatal systemic sequelae resulting from the activity of Shiga toxins. The majority of these infections are caused by E. coli O157:H7 (21,26). This serotype has been frequently isolated from cattle feces, and most human EHEC O157:H7 infections originate, either directly or indirectly, from this source (5, 8). A key step in protecting public health is to know how and where the bacterium persists in this major animal reservoir. Until now, no defined site of colonization by E. coli O157:H7 in the bovine gastrointestinal tract (GIT) has been described, beyond an affinity for the large intestine (17).Enteropathogenic E. coli (EPEC) and most EHEC strains are known to carry a locus of enterocyte effacement (LEE) pathogenicity island (24). This locus encodes a type III secretion system that mediates attachment to mucosal epithelial cells. Injection of effector proteins results in intimate attachment and characteristic attaching and effacing (A/E) lesions dependent on intimin and Tir (translocated intimin receptor) (16,22). E. coli O157:H7 intimately attaches to a variety of cell types and tissues in vitro, and a few studies have demonstrated that E. coli O157:H7 can form A/E lesions ...
SUMMARY The transcytosis of antigens across the gut epithelium by microfold cells (M cells) is important for the induction of efficient immune responses to some mucosal antigens in Peyer’s patches. Recently, substantial progress has been made in our understanding of the factors that influence the development and function of M cells. This review highlights these important advances, with particular emphasis on: the host genes which control the functional maturation of M cells; how this knowledge has led to the rapid advance in our understanding of M-cell biology in the steady-state and during aging; molecules expressed on M cells which appear to be used as “immunosurveillance” receptors to sample pathogenic microorganisms in the gut; how certain pathogens appear to exploit M cells to infect the host; and finally how this knowledge has been used to specifically target antigens to M cells to attempt to improve the efficacy of mucosal vaccines.
A general model of decentralized stochastic control called partial history sharing information structure is presented. In this model, at each step the controllers share part of their observation and control history with each other. This general model subsumes several existing models of information sharing as special cases. Based on the information commonly known to all the controllers, the decentralized problem is reformulated as an equivalent centralized problem from the perspective of a coordinator. The coordinator knows the common information and select prescriptions that map each controller's local information to its control actions. The optimal control problem at the coordinator is shown to be a partially observable Markov decision process (POMDP) which is solved using techniques from Markov decision theory. This approach provides (a) structural results for optimal strategies, and (b) a dynamic program for obtaining optimal strategies for all controllers in the original decentralized problem. Thus, this approach unifies the various ad-hoc approaches taken in the literature. In addition, the structural results on optimal control strategies obtained by the proposed approach cannot be obtained by the existing generic approach (the person-by-person approach) for obtaining structural results in decentralized problems; and the dynamic program obtained by the proposed approach is simpler than that obtained by the existing generic approach (the designer's approach) for obtaining dynamic programs in decentralized problems.
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