Crosspresentation by dendritic cells,”

MHC class I-loading complex A series of endoplasmic reticulum chaperone proteins that stabilize empty MHC class I molecules and control the loading of high-affinity peptides onto MHC class I molecules. Cross-presentation by dendritic cells Abstract | The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8 + T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. Here, we summarize recent advances in our understanding of the intracellular mechanisms of cross-presentation and discuss its role in immunity and tolerance in the context of specialization between DC subsets. Finally, we review current strategies to use cross-presentation for immunotherapy

Efficient and versatile manipulation of the peripheral CD4+ T-cell compartment by antigen targeting to DNGR-1/CLEC9A

DC NK lectin group receptor-1 (DNGR-1, also known as CLEC9A) is a C-type lectin receptor expressed by mouse CD8α+ DC and by their putative equivalents in human. DNGR-1 senses necrosis and regulates CD8+ T-cell cross-priming to dead-cell-associated antigens. In addition, DNGR-1 is a target for selective in vivo delivery of antigens to DC and the induction of CD8+ T-cell and Ab responses. In this study, we evaluated whether DNGR-1 targeting can be additionally used to manipulate antigen-specific CD4+ T lymphocytes. Injection of small amounts of antigen-coupled anti-DNGR-1 mAb into mice promoted MHC class II antigen presentation selectively by CD8α+ DC. In the steady state, this was sufficient to induce proliferation of antigen-specific naïve CD4+ T cells and to drive their differentiation into Foxp3+ regulatory lymphocytes. Co-administration of adjuvants prevented this induction of tolerance and promoted immunity. Notably, distinct adjuvants allowed qualitative modulation of CD4+ T-cell behavior: poly I:C induced a strong IL-12-independent Th1 response, whereas curdlan led to the priming of Th17 cells. Thus, antigen targeting to DNGR-1 is a versatile approach for inducing functionally distinct CD4+ T-cell responses. Given the restricted pattern of expression of DNGR-1 across species, this strategy could prove useful for developing immunotherapy protocols in humans

Limited Foxp3+ Regulatory T Cells Response During Acute Trypanosoma cruzi Infection Is Required to Allow the Emergence of Robust Parasite-Specific CD8+ T Cell Immunity

While it is now acknowledged that CD4+ T cells expressing CD25 and Foxp3 (Treg cells) regulate immune responses and, consequently, influence the pathogenesis of infectious diseases, the regulatory response mediated by Treg cells upon infection by Trypanosoma cruzi was still poorly characterized. In order to understand the role of Treg cells during infection by this protozoan parasite, we determined in time and space the magnitude of the regulatory response and the phenotypic, functional and transcriptional features of the Treg cell population in infected mice. Contrary to the accumulation of Treg cells reported in most chronic infections in mice and humans, experimental T. cruzi infection was characterized by sustained numbers but decreased relative frequency of Treg cells. The reduction in Treg cell frequency resulted from a massive accumulation of effector immune cells, and inversely correlated with the magnitude of the effector immune response as well as with emergence of acute immunopathology. In order to understand the causes underlying the marked reduction in Treg cell frequency, we evaluated the dynamics of the Treg cell population and found a low proliferation rate and limited accrual of peripheral Treg cells during infection. We also observed that Treg cells became activated and acquired a phenotypic and transcriptional profile consistent with suppression of type 1 inflammatory responses. To assess the biological relevance of the relative reduction in Treg cells frequency observed during T. cruzi infection, we transferred in vitro differentiated Treg cells at early moments, when the deregulation of the ratio between regulatory and conventional T cells becomes significant. Intravenous injection of Treg cells dampened parasite-specific CD8+ T cell immunity and affected parasite control in blood and tissues. Altogether, our results show that limited Treg cell response during the acute phase of T. cruzi infection enables the emergence of protective anti-parasite CD8+ T cell immunity and critically influences host resistance

Increasing productivity and improving livelihoods in aquatic agricultural systems: a review of interventions

The doubling of global food demand by 2050 is driving resurgence in interventions for agricultural intensification. Globally, 700 million people are dependent on floodplain or coastal systems. Increased productivity in these aquatic agricultural systems is important for meeting current and future food demand. Agricultural intensification in aquatic agricultural systems has contributed to increased agricultural production, yet these increases have not necessarily resulted in broader development outcomes for those most in need. Here we review studies of interventions that have sought to improve productivity in aquatic agricultural systems in Bangladesh, Cambodia and Zambia. We review evidence of development outcomes from these interventions and the particular role of participatory approaches in intervention design and deployment. There was evidence of increases in productivity in 20 of the 31 studies reviewed. Yet, productivity was only measured beyond the life of the intervention in one case, income and food security improvements were rarely quantified, and the social distribution of benefits rarely described. Participatory approaches were employed in 15 studies, and there was some evidence that development outcomes were more substantial than in cases that were less participatory. To explore the impact of participatory approaches further, we examined five empirical cases. Review and empirical cases provide preliminary evidence suggesting participatory approaches contribute to ensuring agriculture and aquaculture interventions into aquatic agricultural systems may better fit local contexts, are sustained longer, and are more able to deliver development benefits to those most in need. A worthy focus of future research would be comparison between outcomes achieved from interventions with differing levels of participation, and the social differentiation of outcomes