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Blander dendritic

Gaetan Barbet, Leif E Sander, Matthew Geswell, Irina Leonardi, Andrea Cerutti, Iliyan Iliev, J Magarian Blander
Live vaccines historically afford superior protection, yet the cellular and molecular mechanisms mediating protective immunity remain unclear. Here we found that vaccination of mice with live, but not dead, Gram-negative bacteria heightened follicular T helper cell (Tfh) differentiation, germinal center formation, and protective antibody production through the signaling adaptor TRIF. Complementing the dead vaccine with an innate signature of bacterial viability, bacterial RNA, recapitulated these responses...
March 20, 2018: Immunity
J Magarian Blander
Apoptosis is an important component of normal tissue physiology, and the prompt removal of apoptotic cells is equally essential to avoid the undesirable consequences of their accumulation and disintegration. Professional phagocytes are highly specialized for engulfing apoptotic cells. The recent ability to track cells that have undergone apoptosis in situ has revealed a division of labor among the tissue resident phagocytes that sample them. Macrophages are uniquely programmed to process internalized apoptotic cell-derived fatty acids, cholesterol and nucleotides, as a reflection of their dominant role in clearing the bulk of apoptotic cells...
May 2017: Immunological Reviews
Ryan J Cummings, Gaetan Barbet, Gerold Bongers, Boris M Hartmann, Kyle Gettler, Luciana Muniz, Glaucia C Furtado, Judy Cho, Sergio A Lira, J Magarian Blander
Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserves immune self-tolerance and prevents chronic inflammation and autoimmune pathologies. The diverse array of phagocytes that reside within different tissues, combined with the necessarily prompt nature of apoptotic cell clearance, makes it difficult to study this process in situ. The full spectrum of functions executed by tissue-resident phagocytes in response to homeostatic apoptosis, therefore, remains unclear...
November 24, 2016: Nature
J Magarian Blander
MHC class I (MHC-I) molecules are the centerpieces of cross-presentation. They are loaded with peptides derived from exogenous sources and displayed on the plasma membrane to communicate with CD8 T cells, relaying a message of tolerance or attack. The study of cross-presentation has been focused on the relative contributions of the vacuolar versus cytosolic pathways of antigen processing and the location where MHC-I molecules are loaded. While vacuolar processing generates peptides loaded onto vacuolar MHC-I molecules, how and where exogenous peptides generated by the proteasome and transported by TAP meet MHC-I molecules for loading has been a matter of debate...
July 2016: Immunological Reviews
Priyanka Nair-Gupta, Alessia Baccarini, Navpreet Tung, Fabian Seyffer, Oliver Florey, Yunjie Huang, Meenakshi Banerjee, Michael Overholtzer, Paul A Roche, Robert Tampé, Brian D Brown, Derk Amsen, Sidney W Whiteheart, J Magarian Blander
Adaptation of the endoplasmic reticulum (ER) pathway for MHC class I (MHC-I) presentation in dendritic cells enables cross-presentation of peptides derived from phagocytosed microbes, infected cells, or tumor cells to CD8 T cells. How these peptides intersect with MHC-I molecules remains poorly understood. Here, we show that MHC-I selectively accumulate within phagosomes carrying microbial components, which engage Toll-like receptor (TLR) signaling. Although cross-presentation requires Sec22b-mediated phagosomal recruitment of the peptide loading complex from the ER-Golgi intermediate compartment (ERGIC), this step is independent of TLR signaling and does not deliver MHC-I...
July 31, 2014: Cell
Priyanka Nair-Gupta, J Magarian Blander
Cross-presentation involves the presentation of peptides derived from internalized cargo on major histocompatibility complex class I molecules by dendritic cells, a process critical for tolerance and immunity. Detailed studies of the pathways mediating cross-presentation have revealed that this process takes place in a specialized subcellular compartment with a unique set of proteins. In this review, we focus on the recently appreciated role for intracellular vesicular traffic, which serves to equip compartments such as endosomes and phagosomes with the necessary apparatus for conducting the various steps of cross-presentation...
November 22, 2013: Frontiers in Immunology
Meimei Shan, Maurizio Gentile, John R Yeiser, A Cooper Walland, Victor U Bornstein, Kang Chen, Bing He, Linda Cassis, Anna Bigas, Montserrat Cols, Laura Comerma, Bihui Huang, J Magarian Blander, Huabao Xiong, Lloyd Mayer, Cecilia Berin, Leonard H Augenlicht, Anna Velcich, Andrea Cerutti
A dense mucus layer in the large intestine prevents inflammation by shielding the underlying epithelium from luminal bacteria and food antigens. This mucus barrier is organized around the hyperglycosylated mucin MUC2. Here we show that the small intestine has a porous mucus layer, which permitted the uptake of MUC2 by antigen-sampling dendritic cells (DCs). Glycans associated with MUC2 imprinted DCs with anti-inflammatory properties by assembling a galectin-3-Dectin-1-FcγRIIB receptor complex that activated β-catenin...
October 25, 2013: Science
Johan Garaude, J Magarian Blander
The use of innate immune receptor agonists in cancer therapies has suffered from many drawbacks. Our recent observations suggest that some of these hurdles can be overcome by introducing flagellin into tumor cells to promote tumor antigen presentation by dendritic cells (DCs) and simultaneously trigger two types of pattern recognition receptors (PRRs).
September 1, 2012: Oncoimmunology
Priyanka Nair, Derk Amsen, J Magarian Blander
Dendritic cells are innate sentinels of the immune system and potent activators of naÏve T cells. Mechanisms must exist to enable these cells to achieve maximal activation of T cells specific for microbial antigens, while avoiding activation of T cells specific for self-antigens. Here we discuss how a combination of signals from pattern recognition receptors and T cells co-ordinates subcellular trafficking of antigen with both major histocompatibility complex class I and class II molecules and T-cell costimulatory molecules, resulting in the preferential presentation of microbial peptides within a stimulatory context...
December 2011: Traffic
Miriam Beer Torchinsky, J Magarian Blander
In the few years since their discovery, T helper 17 cells (T(H)17) have been shown to play an important role in host defense against infections, and in tissue inflammation during autoimmunity. T(H)17 cells produce IL-17, IL-21, IL-10, and IL-22 cytokines, and thus have broad effects on a variety of tissues. Notably, the requirement for the immunosuppressive cytokine TGF-beta along with the pro-inflammatory cytokine IL-6 for T(H)17 differentiation supports the intimate relationship between the T(H)17 subset and FOXP3(+) regulatory T cells...
May 2010: Cellular and Molecular Life Sciences: CMLS
Miriam Beer Torchinsky, Johan Garaude, Andrea P Martin, J Magarian Blander
Adaptive immune responses rely on differentiation of CD4 T helper cells into subsets with distinct effector functions best suited for host defence against the invading pathogen. Interleukin (IL)-17-producing T helper cells (T(H)17) are a recently identified subset, separate from the T helper type 1 (T(H)1) and T helper type 2 (T(H)2) subsets. Synergy between the cytokines transforming growth factor-beta and IL-6 in vitro induces development of T(H)17 cells in mouse and human systems, whereas IL-23 supports expansion of these cells...
March 5, 2009: Nature
J Magarian Blander
Professional phagocytes play an important role in the clearance of microbial pathogens and apoptotic cells. Many receptors are involved in this process, some with signalling capabilities, some without. Increasing evidence now shows a previously unappreciated regulatory component to phagocytosis exerted by the concomitant engagement of signalling receptors. The engagement of Toll-like receptors (TLRs) during phagocytosis of microbial pathogens is the best characterised example. Here, a brief overview is presented of the findings that TLRs exert positive and phagosome autonomous control on both the kinetics and outcomes of phagosome maturation...
December 2008: Annals of the Rheumatic Diseases
J Magarian Blander
Dendritic cells (DCs) orchestrate either tolerance or immunity. At the heart of this function lies phagocytosis, which allows DCs to sample the tissue microenvironment and deliver both its self and non-self constituents into endocytic compartments for clearance, degradation and presentation by major histocompatibility complex (MHC) molecules. Depending on the type of signalling pathways triggered during phagocytosis, DCs deliver appropriate signals to T cells that determine either their tolerance or activation and differentiation...
February 2007: Cellular Microbiology
J Magarian Blander
Much attention has focused on the role of co-stimulation in dictating tolerance versus immunity to internalized antigens, with the assumption that the presentation of antigen-derived peptides by MHC molecules occurs constitutively. Here, I highlight our new appreciation for the regulated presentation of phagocytosed antigens by MHC class II molecules as a direct result of controlling phagosome maturation by Toll-like receptors. I discuss how the mode of antigen delivery into dendritic cells coupled with the right type of signal transduction pathway can impact greatly not only the co-stimulatory context in which the antigen is presented to naive T cells (signal 2) but MHC-II presentation of the antigen and formation of the T-cell receptor ligand (signal 1) itself...
January 2007: Trends in Immunology
J Magarian Blander, Ruslan Medzhitov
Phagocytosis has essential functions in immunity. Here we highlight the presence of a subcellular level of self-non-self discrimination in dendritic cells that operates at the level of individual phagosomes. We discuss how engagement of Toll-like receptor signaling controls distinct programs of phagosome maturation. An inducible mode of phagosome maturation triggered by these receptors ensures the selection of microbial antigens for presentation by major histocompatibility class II molecules during the simultaneous phagocytosis of self and non-self...
October 2006: Nature Immunology
J Magarian Blander, Ruslan Medzhitov
Dendritic cells constitutively sample the tissue microenvironment and phagocytose both microbial and host apoptotic cells. This leads to the induction of immunity against invading pathogens or tolerance to peripheral self antigens, respectively. The outcome of antigen presentation by dendritic cells depends on their activation status, such that Toll-like receptor (TLR)-induced dendritic cell activation makes them immunogenic, whereas steady-state presentation of self antigens leads to tolerance. TLR-inducible expression of co-stimulatory signals is one of the mechanisms of self/non-self discrimination...
April 6, 2006: Nature
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