Induction of Effective Immunity against Trypanosoma cruzi.

Chagas disease, caused by , is a major public health issue. Limitations in immune responses to natural infection usually result in parasite persistence with significant complications. A safe, effective, and reliable vaccine would reduce the threat of infections; however, no suitable vaccine is currently available due to a lack of understanding of the requirements for induction of fully protective immunity.

Development and Characterization of a Preclinical Model for the Evaluation of CD205-Mediated Antigen Delivery Therapeutics in Type 1 Diabetes.

Dendritic cells (DCs) are crucial for the production of adaptive immune responses to disease-causing microbes. However, in the steady state (i.e.

The negative effect of lipid challenge on autophagy inhibits T cell responses.

Obesity is associated with changes in the immune system that significantly hinder its ability to mount efficient immune responses. Previous studies have reported a dysregulation of immune responses caused by lipid challenge; however, the mechanisms underlying that dysregulation are still not completely understood. Autophagy is an essential catabolic process through which cellular components are degraded by the lysosomal machinery.

The Outcome of the Macrophage Interaction Depends on Phagolysosomal Membrane Integrity.

is a fungal pathogen with worldwide distribution. resides within mature phagolysosomes where it often evades killing and replicates. induces phagolysosomal membrane permeabilization (PMP), but the mechanism for this phenomenon and its consequences for macrophage viability are unknown.

Activation-Induced Autophagy Is Preserved in CD4+ T-Cells in Familial Longevity.

As with many other tissues and organs, the immune system is also affected by age. Immunosenescence is characterized by a decreased ability of immune cells to mount a productive response upon exposure to new antigens. Several studies have reported that members of families with exceptional longevity show improved immune function, which might contribute to the increased life- and health-span observed in those families.

Key roles of autophagy in regulating T-cell function.

In the past 10 years, autophagy has emerged as a crucial regulator of T-cell homeostasis, activation, and differentiation. Through the ability to adjust the cell's proteome in response to different stimuli, different forms of autophagy have been shown to control T-cell homeostasis and survival. Autophagic processes can also determine the magnitude of the T-cell response to TCR engagement, by regulating the cellular levels of specific signaling intermediates and modulating the metabolic output in activated T cells.

Chaperone-mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation.

Chaperone-mediated autophagy (CMA) targets soluble proteins for lysosomal degradation. Here we found that CMA was activated in T cells in response to engagement of the T cell antigen receptor (TCR), which induced expression of the CMA-related lysosomal receptor LAMP-2A. In activated T cells, CMA targeted the ubiquitin ligase Itch and the calcineurin inhibitor RCAN1 for degradation to maintain activation-induced responses.

Proteasomal degradation of Sfp1 contributes to the repression of ribosome biogenesis during starvation and is mediated by the proteasome activator Blm10.

The regulation of ribosomal protein (RP) gene transcription is tightly linked to the nutrient status of the cell and is under the control of metabolic signaling pathways. In Saccharomyces cerevisiae several transcriptional activators mediate efficient RP gene transcription during logarithmic growth and dissociate from RP gene promoters upon nutrient limitation. Repression of RP gene transcription appears to be regulated predominantly by posttranslational modification and cellular localization of transcriptional activators.