Traumatic brain injury (TBI) affects millions annually and is associated with long-term health decline. TBI also shares molecular and cellular hallmarks with neurodegenerative diseases (NDs), typically increasing in prevalence with age, and is a major risk factor for developing neurodegeneration later in life. While our understanding of genes and pathways that underlie neurotoxicity in specific NDs has advanced, we still lack a complete understanding of early molecular and physiological changes that drive neurodegeneration, particularly as an individual ages following a TBI.
View Article and Find Full Text PDFMost metazoans undergo dynamic, circadian-regulated changes in behavior and physiology. Currently, it is unknown how circadian-regulated behavior impacts immunity against infection. Two broad categories of defense against bacterial infection are resistance, control of microbial growth, and tolerance, control of the pathogenic effects of infection.
View Article and Find Full Text PDFCircadian rhythm involves diurnal oscillations in biological processes. In this issue of Cell Host & Microbe, Leone et al. (2015) show that the gut microbiota influences the circadian clock and undergoes circadian oscillations.
View Article and Find Full Text PDFThe contribution of specific factors to bacterial virulence is generally investigated through creation of genetic "knockouts" that are then compared to wild-type strains or complemented mutants. This paradigm is useful to understand the effect of presence vs. absence of a specific gene product but cannot account for concentration-dependent effects, such as may occur with some bacterial toxins.
View Article and Find Full Text PDFSurvival of bacterial infection is the result of complex host-pathogen interactions. An often-overlooked aspect of these interactions is the circadian state of the host. Previously, we demonstrated that Drosophila mutants lacking the circadian regulatory proteins Timeless (Tim) and Period (Per) are sensitive to infection by S.
View Article and Find Full Text PDFOur knowledge of pathogens and symbionts is heavily biased toward phyla containing species that are straightforward to isolate in pure culture. Novel bacterial phyla are often represented by a handful of strains, and the number of species interacting with eukaryotes is likely underestimated. Identification of predicted pathogenesis and symbiosis determinants such as the Type III Secretion System (T3SS) in the genomes of "free-living" bacteria suggests that these microbes participate in uncharacterized interactions with eukaryotes.
View Article and Find Full Text PDFFruit fly immunology is on the verge of an exciting new path. The fruit fly has served as a strong model for innate immune responses; the field is now expanding to use the fruit fly to study pathogenesis. We argue here that, to understand pathogenesis in the fly, we need to understand pathology - and to understand pathology, we need to confront physiology with molecular tools.
View Article and Find Full Text PDFWe showed previously that eiger, the Drosophila tumor necrosis factor homolog, contributes to the pathology induced by infection with Salmonella typhimurium. We were curious whether eiger is always detrimental in the context of infection or if it plays a role in fighting some types of microbes. We challenged wild-type and eiger mutant flies with a collection of facultative intracellular and extracellular pathogens, including a fungus and Gram-positive and Gram-negative bacteria.
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