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Tubercule granulomas are thought to be tightly sealed compartments that keep mycobacteria sequestered and inactive. Ramakrishnan and colleagues p (828; News and Views by Flynn p 778) have tested this using in vivo granuloma models of tuberculosis. Superinfections of mycobacteria (green rods) were found to invade and multiply in previously established granulomas (spaces with red rods), indicating that granulomas could be inadvertently providing a 'safe haven' for these agents of chronic infection. Artwork by Lewis Long.
As part of the national effort in the US to protect civilians from bioterrorist attacks, the US National Institute of Allergy and Infectious Diseases (NIAID) was charged with the development of diverse research resources. The NIAID Resources for Biodefense Research program is forging new collaborations between immunologists and infectious disease experts and is reinvigorating research in the general area of immune protection against pathogenic infection.
The combination of bioinformatic and biological approaches constitutes a powerful method for identifying gene regulatory elements. High-quality genome sequences are available in public databases for several vertebrate species. Comparative cross-species sequence analysis of these genomes shows considerable conservation of noncoding sequences in DNA. Biological analyses show that an unexpectedly high number of the conserved sequences correspond to functional cis-regulatory regions that influence gene transcription. Because research biologists are often unfamiliar with the bioinformatic resources at their disposal, this commentary discusses how to integrate biological and bioinformatic methods in the discovery of gene regulatory regions and includes a tutorial on widely available comparative genomics programs.
Antimicrobial peptides are essential effectors of gut immunity. The cryptdin-related sequence peptides represent a newly identified large family of antimicrobial peptides that form dimers to increase diversity.
Many patients with Crohn disease, an inflammatory bowel disorder, carry mutations in NOD2. The finding that NOD2 normally dampens Toll-like receptor 2–mediated inflammation may explain this association.
Granulomas are thought to be immunological barriers that effectively contain mycobacteria. This hypothesis is now challenged by data that show granulomas are dynamic entities permissive to bacterial latency and reinfection.
A handful of agonist peptide–MHC complexes can evoke a sustained signal from the T cell receptor. A combination of mathematical models and imaging experiments suggests a key function for CD4 and endogenous (self) peptides in the generation of this sensitive response.