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SPOTLIGHT

Articles of Significant Interest Selected from This Issue by the Editors

Bacillus anthracis produces two bipartite toxins, edema toxin (ET) and lethal toxin (LT). In the first animal study using both toxins in a highly purified form, Firoved et al. (p. 2120-2125) report that pretreatment or concomitant treatment of anthrax LT-resistant DBA/2J mice with sublethal doses of ET sensitizes the mice to LT lethality. This is the first report of synergistic action for these major anthrax virulence factors.

Natural Mutants of Toxoplasma gondii Provide a Model for Development and Transmission

The pathogenesis of Toxoplasma gondii food-borne illness is due to the ability of semidormant tissue cysts to cause oral infection following ingestion of cysts in undercooked meat. Efficient oral transmission has been linked to the extremely broad host range of T. gondii, which includes many wild and domestic animals. Fux et al. (p. 2580-2590) identify a number of natural variants of the parasite that have diminished or absent transmission following oral challenge in the mouse model. Analysis of these strains reveals that they fail to undergo differentiation in response to stress and that they form underdeveloped or defective cysts. Identifying the molecular basis of these defects may aid in the definition of adaptations that are important for transmission and in efforts to prevent infection.

Intestinal Epithelial Cells Increase Expression of Toll-Like Receptor 9 in Response to Pathogenic Bacterial DNA

Colonic epithelial cells are constantly exposed to high levels of bacteria and to bacterial DNA. Intestinal cells must recognize and respond appropriately to pathogens while maintaining tolerance to nonpathogenic commensal bacteria. Toll-like receptor responses in intestinal epithelial cells are polarized, and their activation plays an essential role in maintaining colonic homeostasis. Ewaschuk et al. (p. 2572-2579) show that intestinal epithelial cells increase surface localization and expression of Toll-like receptor 9 (TLR9) in response to DNA from pathogenic bacterial strains but not in response to DNA from probiotic strains. This suggests that the epithelial inflammatory response to pathogenic bacterial DNA is mediated at least in part by increased TLR9 expression and altered localization.

Role of Natural Killer T Cells in Murine Schistosomiasis

Natural killer T (NKT) cells are innate/memory immune cells that express semi-invariant (iNKT) or more-diverse (non-iNKT) T-cell receptors. Although their role in autoimmune and inflammatory diseases, cancer, and infection has largely been described, no study has addressed the role of NKT cells in metazoan parasite infections. Mallevaey et al. (p. 2171-2180) demonstrate that both iNKT and non-iNKT cells become activated during the course of murine schistosomiasis and suggest that these subsets have opposite and perhaps complementary functions in the Th1/Th2 balance of the immune response. These findings underline the need to study these cells during other helminth infections that affect human populations.

Anti-Toxin-Based Enterotoxigenic Escherichia coli Vaccine in a Patch: Exceeding Postchallenge and Oral Vaccine Immunity Benchmarks

Enterotoxigenic Escherichia coli (ETEC) is a toxin-based diarrheal disease caused by heat-labile enterotoxin (LT). Use of LT as a vaccine antigen is hampered because LT cannot be given safely orally or nasally. Glenn et al. (p. 2163-2170) show that LT delivered in a patch after modest skin pretreatment is safe and highly immunogenic. Anti-LT immune responses to 50 µg of LT delivered by patch exceed responses obtained after human challenge with virulent live infectious ETEC, as well as those elicited by use of the oral cholera B subunit vaccine. These findings indicate that an LT-based vaccine patch induces robust toxin-based immunity that compares well with natural and effective field immunity.

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