Unlabelled: Infection with the apicomplexan parasite is a leading cause of diarrheal disease. Cryptosporidiosis is of particular importance in infants and shows a strong association with malnutrition, both as a risk factor and as a consequence. invades and replicates within the small intestine epithelial cells.
View Article and Find Full Text PDFCryptosporidium is an enteric pathogen and a prominent cause of diarrheal disease worldwide. Control of Cryptosporidium requires CD4+ T cells, but how protective CD4+ T cell responses are generated is poorly understood. Here, Cryptosporidium parasites that express MHCII-restricted model antigens were generated to understand the basis for CD4+ T cell priming and effector function.
View Article and Find Full Text PDFThe production of IFN-γ is crucial for control of multiple enteric infections, but its impact on intestinal epithelial cells (IEC) is not well understood. Cryptosporidium parasites exclusively infect epithelial cells and the ability of interferons to activate the transcription factor STAT1 in IEC is required for parasite clearance. Here, the use of single cell RNA sequencing to profile IEC during infection revealed an increased proportion of mid-villus enterocytes during infection and induction of IFN-γ-dependent gene signatures that was comparable between uninfected and infected cells.
View Article and Find Full Text PDFThe production of IFN-γ is crucial for control of multiple enteric infections, but its impact on intestinal epithelial cells (IEC) is not well understood. parasites exclusively infect epithelial cells and the ability of interferons to activate the transcription factor STAT1 in IEC is required for parasite clearance. The use of single cell RNA sequencing to profile IEC during infection revealed induction of IFN-γ-dependent gene signatures that was comparable between uninfected and infected cells, and IEC expression of the IFN-γ receptor was required for parasite control.
View Article and Find Full Text PDFis an enteric pathogen that is a prominent cause of diarrheal disease. Control of this infection requires CD4 T cells, though the processes that lead to T cell-mediated resistance have been difficult to assess. Here, parasites that express MHCII-restricted model antigens were generated to dissect the early events that influence CD4 T cell priming and effector function.
View Article and Find Full Text PDFCryptosporidium parasites replicate within intestinal epithelial cells and are an important cause of diarrhoeal disease in young children and in patients with primary and acquired defects in T cell function. This Review of immune-mediated control of Cryptosporidium highlights advances in understanding how intestinal epithelial cells detect this infection, the induction of innate resistance and the processes required for activation of T cell responses that promote parasite control. The development of a genetic tool set to modify Cryptosporidium combined with tractable mouse models provide new opportunities to understand the principles that govern the interface between intestinal epithelial cells and the immune system that mediate resistance to enteric pathogens.
View Article and Find Full Text PDFcauses debilitating diarrheal disease in patients with primary and acquired defects in T cell function. However, it has been a challenge to understand how this infection generates T cell responses and how they mediate parasite control. Here, was engineered to express a parasite effector protein (MEDLE-2) that contains the MHC-I restricted SIINFEKL epitope which is recognized by TCR transgenic OT-I CD8 T cells.
View Article and Find Full Text PDFCryptosporidium is a leading cause of diarrheal disease in children and an important contributor to early childhood mortality. The parasite invades and extensively remodels intestinal epithelial cells, building an elaborate interface structure. How this occurs at the molecular level and the contributing parasite factors are largely unknown.
View Article and Find Full Text PDF-myristoylation is a ubiquitous class of protein lipidation across eukaryotes and -myristoyl transferase (NMT) has been proposed as an attractive drug target in several pathogens. Myristoylation often primes for subsequent palmitoylation and stable membrane attachment, however, growing evidence suggests additional regulatory roles for myristoylation on proteins. Here we describe the myristoylated proteome of using chemoproteomic methods and show that a small-molecule NMT inhibitor developed against related .
View Article and Find Full Text PDFToxoplasma gondii parasites rapidly exit their host cell when exposed to calcium ionophores. Calcium-dependent protein kinase 3 (TgCDPK3) was previously identified as a key mediator in this process, as TgCDPK3 knockout (∆cdpk3) parasites fail to egress in a timely manner. Phosphoproteomic analysis comparing WT with ∆cdpk3 parasites revealed changes in the TgCDPK3-dependent phosphoproteome that included proteins important for regulating motility, but also metabolic enzymes, indicating that TgCDPK3 controls processes beyond egress.
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