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https://www.readbyqxmd.com/read/29142130/effective-priming-of-hsv-specific-cd8-t-cells-in-vivo-does-not-require-infected-dendritic-cells
#1
Paul G Whitney, Christina Makhlouf, Beth MacLeod, Joel Z Ma, Elise Gressier, Marie Greyer, Katharina Hochheiser, Annabell Bachem, Ali Zaid, David Voehringer, William R Heath, Mayura V Wagle, Ian Parish, Tiffany A Russell, Stewart A Smith, David C Tscharke, Thomas Gebhardt, Sammy Bedoui
Resolution of virus infections depends on the priming of virus-specific CD8(+) T cells by dendritic cells (DC). While this process requires MHC class I-restricted antigen presentation by DC, the relative contribution to CD8(+) T cell priming by infected DC is less clear. We have addressed this question in the context of a peripheral infection with herpes simplex virus type 1 (HSV). Assessing the endogenous, polyclonal HSV-specific CD8(+) T cell response, we found that effective in vivo T cell priming depended on the presence of DC subsets specialized in cross-presentation while Langerhans cells and plasmacytoid DC were dispensable...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29141870/ig%C3%AE-ubiquitination-activates-pi3k-signals-required-for-endosomal-sorting
#2
Margaret Veselits, Azusa Tanaka, Yaoqing Chen, Keith Hamel, Malay Mandal, Matheswaran Kandasamy, Balaji Manicassamy, Shannon K O'Neill, Patrick Wilson, Roger Sciammas, Marcus R Clark
A wealth of in vitro data has demonstrated a central role for receptor ubiquitination in endocytic sorting. However, how receptor ubiquitination functions in vivo is poorly understood. Herein, we report that ablation of B cell antigen receptor ubiquitination in vivo uncouples the receptor from CD19 phosphorylation and phosphatidylinositol 3-kinase (PI3K) signals. These signals are necessary and sufficient for accumulating phosphatidylinositol (3,4,5)-trisphosphate (PIP3) on B cell receptor-containing early endosomes and proper sorting into the MHC class II antigen-presenting compartment (MIIC)...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29136276/targeted-therapies-immunologic-effects-and-potential-applications-outside-of-cancer
#3
REVIEW
Anna E Kersh, Spencer Ng, Yun Min Chang, Maiko Sasaki, Susan N Thomas, Haydn T Kissick, Gregory B Lesinski, Ragini R Kudchadkar, Edmund K Waller, Brian P Pollack
Two pharmacologic approaches that are currently at the forefront of treating advanced cancer are those that center on disrupting critical growth/survival signaling pathways within tumor cells (commonly referred to as "targeted therapies") and those that center on enhancing the capacity of a patient's immune system to mount an antitumor response (immunotherapy). Maximizing responses to both of these approaches requires an understanding of the oncogenic events present in a given patient's tumor and the nature of the tumor-immune microenvironment...
November 14, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29133913/nitric-oxide-mediated-inhibition-of-antigen-presentation-from-dcs-to-cd4-t-cells-in-cancer-and-measurement-of-stat1-nitration
#4
Joseph Markowitz, Jiang Wang, Zach Vangundy, Jia You, Vedat Yildiz, Lianbo Yu, Isaac P Foote, Owen E Branson, Andrew R Stiff, Taylor R Brooks, Brandon Biesiadecki, Thomas Olencki, Susheela Tridandapani, Michael A Freitas, Tracey Papenfuss, Mitch A Phelps, William E Carson
Myeloid derived suppressor cells (MDSC) produce nitric oxide (NO) and inhibit dendritic cell (DC) immune responses in cancer. DCs present cancer cell antigens to CD4(+) T cells through Jak-STAT signal transduction. In this study, NO donors (SNAP and DETA-NONOate) inhibited DC antigen presentation. As expected, MDSC isolated from peripheral blood mononuclear cells (PBMC) from cancer patients produced high NO levels. We hypothesized that NO producing MDSC in tumor-bearing hosts would inhibit DC antigen presentation...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133898/intertwining-dna-rna-nanocapsules-loaded-with-tumor-neoantigens-as-synergistic-nanovaccines-for-cancer-immunotherapy
#5
Guizhi Zhu, Lei Mei, Harshad D Vishwasrao, Orit Jacobson, Zhantong Wang, Yijing Liu, Bryant C Yung, Xiao Fu, Albert Jin, Gang Niu, Qin Wang, Fuwu Zhang, Hari Shroff, Xiaoyuan Chen
Nanomedicines that co-deliver DNA, RNA, and peptide therapeutics are highly desirable yet remain underdeveloped for cancer theranostics. Herein, we report self-assembled intertwining DNA-RNA nanocapsules (iDR-NCs) that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as tumor-specific peptide neoantigens into antigen presenting cells (APCs) in lymph nodes for cancer immunotherapy. These nanovaccines were prepared by (1) producing tandem CpG and shRNA via concurrent rolling circle replication and rolling circle transcription, (2) self-assembling CpG and shRNA into DNA-RNA microflowers, (3) shrinking microflowers into iDR-NCs using PEG-grafted cationic polypeptides, and (4) physically loading neoantigen into iDR-NCs...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29133348/non-pathogenic-colonization-with-chlamydia-in-the-gastrointestinal-tract-as-oral-vaccination-for-inducing-transmucosal-protection
#6
Luying Wang, Cuiming Zhu, Tianyuan Zhang, Qi Tian, Nu Zhang, Sandra Morrison, Richard Morrison, Min Xue, Guangming Zhong
Chlamydia has been detected in the gastrointestinal tracts of humans and animals. We now report that gastrointestinal Chlamydia muridarum is able to induce robust transmucosal protection in mice. C. muridarum colonization in the gastrointestinal tract correlated with both a shortened course of C. muridarum genital infection and stronger protection against subsequent genital tract challenge infection. Mice pre-inoculated intragastrically with C. muridarum became highly resistant to subsequent C. muridarum infection in the genital tract, resulting in prevention of pathology in the upper genital tract...
November 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29133346/mycobacterium-tuberculosis-groel2-modulates-dendritic-cell-responses
#7
Maria Georgieva, Jonathan Kevin Sia, Erica Bizzell, Ranjna Madan-Lala, Jyothi Rengarajan
Mycobacterium tuberculosis (Mtb) successfully subverts the host immune response to promote disease progression. In addition to its known intracellular niche in macrophages, Mtb interferes with the functions of dendritic cells (DCs), which are the primary antigen presenting cells in the immune system. We previously showed that Mtb dampens proinflammatory responses and impairs DC functions through the cell envelope-associated serine protease, Hip1. Here we present data showing that Mtb GroEL2, a substrate of Hip1, modulates DC functions...
November 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29129918/intratumoral-cd40-activation-and-checkpoint-blockade-induces-t-cell-mediated-eradication-of-melanoma-in-the-brain
#8
Manisha Singh, Christina Vianden, Mark J Cantwell, Zhimin Dai, Zhilan Xiao, Meenu Sharma, Hiep Khong, Ashvin R Jaiswal, Faisal Faak, Yared Hailemichael, L M E Janssen, Uddalak Bharadwaj, Michael A Curran, Adi Diab, Roland L Bassett, David J Tweardy, Patrick Hwu, Willem W Overwijk
CD40 agonists bind the CD40 molecule on antigen-presenting cells and activate them to prime tumor-specific CD8(+) T cell responses. Here, we study the antitumor activity and mechanism of action of a nonreplicating adenovirus encoding a chimeric, membrane-bound CD40 ligand (ISF35). Intratumoral administration of ISF35 in subcutaneous B16 melanomas generates tumor-specific, CD8(+) T cells that express PD-1 and suppress tumor growth. Combination therapy of ISF35 with systemic anti-PD-1 generates greater antitumor activity than each respective monotherapy...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29129651/dendritic-cells-in-the-cornea-during-herpes-simplex-viral-infection-and-inflammation
#9
REVIEW
Min S Kwon, Nicole A Carnt, Naomi R Truong, Ushasree Pattamatta, Andrew J White, Chameen Samarawickrama, Anthony L Cunningham
Herpes simplex keratitis is commonly caused by Herpes simplex Virus Type 1 (HSV-1), which primarily infects eyelids, corneas or conjunctiva. HSV-1- through sophisticated interactions with dendritic cells (DCs), a type of antigen-presenting cell)-initiates pro-inflammatory responses in the cornea. Corneas were once thought to be an immune privileged region; however, with the recent discovery of DCs that reside in the cornea, this long held conjecture has been overturned. Therefore, evaluating the clinical, preclinical, and cell-based studies that investigate the roles of DCs in corneas infected with HSV is critical...
November 9, 2017: Survey of Ophthalmology
https://www.readbyqxmd.com/read/29129023/pathomechanisms-of-contact-sensitization
#10
REVIEW
Philipp R Esser, Stefan F Martin
Contact sensitization is the initial process involved in the development of an allergic reaction to xenobiotic environmental substances. Here, we briefly describe the differences between irritant and allergic contact dermatitis. Then, we highlight the essential steps involved in the development of an ACD reaction, i.e., the protein binding of haptens, genetic factors influencing the penetration of sensitizers into the skin, the different mechanisms driving the initial development of an inflammatory cytokine micromilieu enabling the full maturation of dendritic cells, the role of pre- and pro-haptens, antigen presentation and T cell activation via MHC and CD1 molecules, dendritic cell (DC) migration, and potential LC contribution as well as the different T cell subsets involved in ACD...
November 11, 2017: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/29128232/liposome-based-immunity-inducing-systems-for-cancer-immunotherapy
#11
REVIEW
Eiji Yuba
Cancer immunotherapy has gained much attention for next-generation cancer treatment. To conduct cancer immunotherapy, efficient antigen delivery systems must be able to deliver an antigen selectively to antigen-presenting cells, release it at suitable sites for induction of cross-presentation, and simultaneously induce activation of immunocompetent cells. Liposomes are a candidate for use as such multifunctional antigen delivery carriers because of their capability for easy functionalization. This review describes the rational design of liposome-based antigen delivery systems...
November 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29126878/dendritic-cells-in-systemic-sclerosis-advances-from-human-and-mice-studies
#12
REVIEW
Alsya J Affandi, Tiago Carvalheiro, Timothy R D J Radstake, Wioleta Marut
Systemic sclerosis (SSc) is a complex heterogeneous fibrotic autoimmune disease with an unknown exact etiology, and characterized by three hallmarks: fibrosis, vasculopathy, and immune dysfunction. Dendritic cells (DCs) are specialized cells in pathogen sensing with high potency of antigen presentation and capable of releasing mediators to shape the immune response. Altered DCs distributions and their impaired functions may account for their role in breaking the immune tolerance and driving inflammation in SSc, and the direct contribution of DCs in promoting endothelial dysfunction and fibrotic process has only begun to be understood...
November 7, 2017: Immunology Letters
https://www.readbyqxmd.com/read/29126597/role-of-autophagy-in-mhc-class-i-restricted-antigen-presentation
#13
Luc Van Kaer, Vrajesh V Parekh, J Luke Postoak, Lan Wu
Major histocompatibility complex (MHC) class I molecules present peptide antigens to MHC class I-restricted CD8(+) T lymphocytes. The peptides loaded onto MHC class I molecules are typically derived from cytosolic antigens, which includes both self and foreign proteins. In addition to this classical MHC class I antigen presentation pathway, some cell types, especially dendritic cells can present antigens from exogenous sources to MHC class I-restricted CD8(+) T cells, in a process called cross-presentation...
November 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29125738/profiling-of-protein-o-glcnacylation-in-murine-cd8-effector-and-memory-like-t-cells
#14
Aime Lopez Aguilar, Yu Gao, Xiaomeng Hou, Gregoire Lauvau, John R Yates, Peng Wu
During an acute infection, antigenic stimulation leads to activation, expansion, and differentiation of naïve CD8(+) T cells, first into cytotoxic effector cells and eventually into long-lived memory cells. T cell antigen receptors (TCRs) detect antigens on antigen-presenting cells (APCs) in the form of antigenic peptides bound to major histocompatibility complex I (MHC-I)-encoded molecules and initiate TCR signal transduction network. This process is mediated by phosphorylation of many intracellular signaling proteins...
November 10, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29125185/thymus-involvement-in-early-onset-myasthenia-gravis
#15
REVIEW
Mélanie A Cron, Solène Maillard, José Villegas, Frédérique Truffault, Muriel Sudres, Nadine Dragin, Sonia Berrih-Aknin, Rozen Le Panse
It has long been established that the thymus plays a central role in autoimmune myasthenia gravis (MG) because of either thymoma or thymic hyperplasia of lymphoproliferative origin. In this review, we discuss thymic changes associated with thymic hyperplasia and their implications in the development of an autoimmune response against the acetylcholine receptor (AChR).The hyperplastic MG thymus displays all the characteristics of tertiary lymphoid organs (TLOs): neoangiogenic processes with high endothelial venule and lymphatic vessel development, chemokine overexpression favoring peripheral cell recruitment, and ectopic germinal center development...
November 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29124321/vaccine-responses-in-newborns
#16
REVIEW
Anja Saso, Beate Kampmann
Immunisation of the newborn represents a key global strategy in overcoming morbidity and mortality due to infection in early life. Potential limitations, however, include poor immunogenicity, safety concerns and the development of tolerogenicity or hypo-responsiveness to either the same antigen and/or concomitant antigens administered at birth or in the subsequent months. Furthermore, the neonatal immunological milieu is polarised towards Th2-type immunity with dampening of Th1-type responses and impaired humoral immunity, resulting in qualitatively and quantitatively poorer antibody responses compared to older infants...
November 9, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/29124315/the-class-i-iv-hdac-inhibitor-mocetinostat-increases-tumor-antigen-presentation-decreases-immune-suppressive-cell-types-and-augments-checkpoint-inhibitor-therapy
#17
David Briere, Niranjan Sudhakar, David M Woods, Jill Hallin, Lars D Engstrom, Ruth Aranda, Harrah Chiang, Andressa L Sodré, Peter Olson, Jeffrey S Weber, James G Christensen
Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immune cells...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29123650/transcellular-communication-at-the-immunological-synapse-a-vesicular-traffic-mediated-mutual-exchange
#18
REVIEW
Francesca Finetti, Chiara Cassioli, Cosima T Baldari
The cell's ability to communicate with the extracellular environment, with other cells, and with itself is a crucial feature of eukaryotic organisms. In the immune system, T lymphocytes assemble a specialized structure upon contact with antigen-presenting cells bearing a peptide-major histocompatibility complex ligand, known as the immunological synapse (IS). The IS has been extensively characterized as a signaling platform essential for T-cell activation. Moreover, emerging evidence identifies the IS as a device for vesicular traffic-mediated cell-to-cell communication as well as an active release site of soluble molecules...
2017: F1000Research
https://www.readbyqxmd.com/read/29123530/human-cardiac-derived-stem-progenitor-cells-fine-tune-monocyte-derived-descendants-activities-toward-cardiac-repair
#19
Noémie Dam, Hocine Rachid Hocine, Itziar Palacios, Olga DelaRosa, Ramón Menta, Dominique Charron, Armand Bensussan, Hicham El Costa, Nabila Jabrane-Ferrat, Wilfried Dalemans, Eleuterio Lombardo, Reem Al-Daccak
Cardiac repair following MI relies on a finely regulated immune response involving sequential recruitment of monocytes to the injured tissue. Monocyte-derived cells are also critical for tissue homeostasis and healing process. Our previous findings demonstrated the interaction of T and natural killer cells with allogeneic human cardiac-derived stem/progenitor cells (hCPC) and suggested their beneficial effect in the context of cardiac repair. Therefore, we investigated here whether monocytes and their descendants could be also modulated by allogeneic hCPC toward a repair/anti-inflammatory phenotype...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29123522/transcriptome-analysis-of-circulating-immune-cell-subsets-highlight-the-role-of-monocytes-in-zaire-ebola-virus-makona-pathogenesis
#20
Andrea R Menicucci, Krista Versteeg, Courtney Woolsey, Chad E Mire, Joan B Geisbert, Robert W Cross, Krystle N Agans, Allen Jankeel, Thomas W Geisbert, Ilhem Messaoudi
Existing models of Ebola virus disease (EVD) suggest antigen-presenting cells are initial targets of Zaire ebolavirus (ZEBOV). In vitro studies have shown that ZEBOV infection of monocytes and macrophages results in the production of inflammatory mediators, which may cause lymphocyte apoptosis. However, these findings have not been corroborated by in vivo studies. In this study, we report the first longitudinal analysis of transcriptional changes in purified monocytes, T-cells, and B-cells isolated from cynomolgus macaques following infection with ZEBOV-Makona...
2017: Frontiers in Immunology
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