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Immunology and Cell Biology

Michelle Brault, Andrew Oberst
Necroptosis is a lytic form of programmed cell death that involves the swelling and rupture of dying cells. While several necroptosis-inducing stimuli have been defined, in most cells this pathway is kept in check by the action of the pro-apoptotic protease caspase-8 and the IAP ubiquitin ligases. How and when necroptosis is triggered under physiological conditions therefore remains a persistent question. Because necroptosis likely arose as a defensive mechanism against viral infection, exploration of this question requires a consideration of host-pathogen interactions, and how the sensing of infection could sensitize cells to necroptosis...
December 2, 2016: Immunology and Cell Biology
Lazaros Vasilikos, Lisanne M Spilgies, Janin Knop, WWei-Lynn Wong
Understanding how Inhibitors of APoptosis proteins (IAPs) regulate apoptosis and necroptosis has been fast-forwarded by the use of Smac mimetics to deplete or inhibit the IAPs, specifically cIAP1& 2 and XIAP. The loss or inhibition of cIAP1, cIAP2 and XIAP causes the majority of cells to be sensitized to death receptor induced cell death, particularly tumour necrosis factor (TNF). Mouse genetics shows that there is some functional redundancy and the use of Smac mimetics has allowed us to understand how changing the composition of proteins recruited to TNF receptor 1 upon TNF ligation can alter protein complex formation and activation of apoptosis or necroptosis, particularly when caspases are inhibited...
December 1, 2016: Immunology and Cell Biology
Xin M Wang, Lauren E Holz, Sumaiya Chowdhury, Shaun P Cordoba, Kathryn A Evans, Margaret G Gall, Ana Júlia Vieira de Ribeiro, Yuan Zhou Zheng, Miriam T Levy, Denise M T Yu, Tsun-Wen Yao, Natasa Polak, Christopher J Jolly, Patrick Bertolino, Geoffrey W McCaughan, Mark D Gorrell
Liver fibrosis is a progressive pathological process involving inflammation and extracellular matrix deposition. Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a cell surface glycoprotein and serine protease. DPP4 binds to fibronectin, can inactivate specific chemokines, incretin hormone and neuropeptides, and influences cell adhesion and migration. Such properties suggest a pro-fibrotic role for this peptidase but this hypothesis needs in vivo examination. Experimental liver injury was induced with carbon tetrachloride (CCl4) in DPP4 gene knockout (gko) mice...
November 30, 2016: Immunology and Cell Biology
Janin Chandra, Paula T Y Kuo, Anne M Hahn, Gabrielle T Belz, Ian H Frazer
Batf3 is a transcription factor that impacts the development of CD103(+) tissue-resident dendritic cells (DCs). However, whether Batf3 is absolutely required for the development of CD8(+) DCs remains controversial. Id2 is required for CD8(+) DC development. Here we show that bone marrow chimeric mice with a deletion of Id2 in the CD11c compartment lose the ability to reject a skin graft expressing a non-self protein antigen or mount a delayed hypersensitivity response. In contrast, Batf3((-/-)) mice remained competent for skin graft rejection and delayed hypersensitivity, and retained a CD8(+) DC population with markers characteristic of the CD11b(+) DC lineage, including CD11b, CD4 and CD172α, as well as the key regulator transcription factor IRF4, but lacked IRF8 expression...
November 29, 2016: Immunology and Cell Biology
Christian Büll, Estel Collado-Camps, Esther D Kers-Rebel, Torben Heise, Jonas N Søndergaard, Martijn H den Brok, Barbara M Schulte, Thomas J Boltje, Gosse J Adema
Sialic acid sugars cover the surface of dendritic cells (DCs) and have been suggested to impact several aspects of DC biology. Research into the role of sialic acids in DCs, however, is complicated by the limited number of tools available to modulate sialic acid expression. Here we report on a synthetic, fluorinated sialic acid mimetic, Ac53FaxNeu5Ac, which potently blocks sialic acid expression in human monocyte-derived DCs (moDCs). Sialic acid blockade enhanced the responsiveness of moDCs to Toll-like receptor (TLR) stimulation as measured by increased maturation marker expression and cytokine production...
November 22, 2016: Immunology and Cell Biology
Sean Nelson, Hiroshi Kiyono, Yosuke Kurashima
No abstract text is available yet for this article.
November 22, 2016: Immunology and Cell Biology
Omar A Alcaráz-López, Cindy García-Gil, Claudia Morales-Martínez, Gonzalo López-Rincón, Ciro Estrada-Chávez, José A Gutiérrez-Pabello, Hugo Esquivel-Solís
Mycobacterium bovis, the causative agent of bovine tuberculosis (BTB), is a successful pathogen that remains an important global threat to livestock. Cattle naturally exposed to M. bovis normally become reactive to the M. bovis-purified protein derivative (PPD; tuberculin) skin test; however, some individuals remain negative, suggesting they may be resistant to infection. To better understand host innate resistance to infection, 26 cattle from herds with a long history of high tuberculosis prevalence were included in this study...
November 11, 2016: Immunology and Cell Biology
Meghan Bliss-Moreau, Alyce A Chen, Akshay D'Cruz, Ben A Croker
Immunological responses activated by pathogen recognition come in many guises. The proliferation, differentiation, and recruitment of immune cells, and the production of inflammatory cytokines and chemokines are central to lifelong immunity. Cell death serves as a key function in the resolution of innate and adaptive immune responses. It also coordinates cell-intrinsic effector functions to restrict infection. Necrosis was formally considered a passive form of cell death or a consequence of pathogen virulence factor expression, and necrotic tissue was associated with infection...
November 9, 2016: Immunology and Cell Biology
Angelika Peruń, Rafał Biedroń, Maciej K Konopiński, Anna Białecka, Janusz Marcinkiewicz, Szczepan Józefowski
Scavenger receptor (SR)-mediated, opsonin-independent phagocytosis of bacteria by macrophages has been suggested to represent an important, early mechanism of anti-bacterial host defense. However, although the ability to bind bacteria has been demonstrated to be a shared feature of all types of SRs, in many cases the evidence is limited to the demonstration of increased binding of killed, fluorescently-labeled bacteria to non-phagocytic cells transfected with these receptors. We sought to verify the ability of SRs to mediate non-opsonic phagocytosis of live Escherichia coli (Ec) and Staphylococcus aureus (Sa), model species of Gram-negative and -positive bacteria, respectively, and to assess relative contributions of different SRs expressed on murine macrophages in this process...
November 9, 2016: Immunology and Cell Biology
Justyna Rak, Simón Méndez-Ferrer
No abstract text is available yet for this article.
November 8, 2016: Immunology and Cell Biology
Nadine Hartmann, Mitchell Kronenberg
No abstract text is available yet for this article.
November 8, 2016: Immunology and Cell Biology
Yann Gallais, Natacha Szely, François-Xavier Legrand, Arnaud Leroy, Marc Pallardy, Isabelle Turbica
Patients treated with therapeutic biological products (BP) frequently develop anti-drug antibodies (ADA) with potential neutralizing capacities leading to loss of clinical response or serious side effects. BP aggregates have been suggested to promote immunogenicity, thus enhancing ADA production. Dendritic cells (DC) are key effectors in T-cell and B-cell fates, and the subsequent generation of immunogenicity. The objective of this work was to determine if BP aggregates can participate to DC maturation and T-cell activation...
November 8, 2016: Immunology and Cell Biology
Sachin Sharma, Thomas Kaufmann, Subhrajit Biswas
The routes leading to programmed cell death are as tightly regulated as those of cellular growth and proliferation, and a finely synchronized balance between the life and death of cells ensures proper organ size and function. Inhibitors of apoptosis (IAPs) proteins were initially characterized by their ability to directly bind and inhibit apoptotic caspases. However, recent studies have clarified that IAPs are much more functionally versatile, modulating a vast range of signaling pathways that have an impact on antimicrobial responses, tumorigenesis, metastasis and cellular migration...
November 8, 2016: Immunology and Cell Biology
Tamsin Dockree, Christopher J Holland, Mathew Clement, Kristin Ladell, James E McLaren, Hugo A van den Berg, Emma Gostick, Kelly L Miners, Sian Llewellyn-Lacey, John S Bridgeman, Stephen Man, Mick Bailey, Scott R Burrows, David A Price, Linda Wooldridge
The CD8 co-receptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR)-binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8(+) T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude. However, recognition specificity is lost altogether with more substantial increases in pMHCI/CD8 affinity (~10-fold)...
November 8, 2016: Immunology and Cell Biology
Lis N Velásquez, M Ayelén Milillo, M Victoria Delpino, Aldana Trotta, M Florencia Mercogliano, Roberto G Pozner, Roxana Schillaci, Patricia V Elizalde, Guillermo H Giambartolomei, Paula Barrionuevo
Brucella abortus is able to persist inside the host despite the development of potent CD8(+) T cell responses. We have recently reported the ability of B. abortus to inhibit the IFN-γ-induced MHC-I cell surface expression on human monocytes. This phenomenon was due to the B. abortus-mediated retention of MHC-I molecules within the Golgi apparatus and was dependent on bacterial viability. However, the implications of bacterial virulence or replicative capacity and the signaling pathways remained unknown. Here, we demonstrated that the B...
November 4, 2016: Immunology and Cell Biology
Jie Luo, Yuejin Liang, Fanping Kong, Jingfan Qiu, Xinjian Liu, Ailing Chen, Bruce A Luxon, Hannah W Wu, Yong Wang
BACKGROUND: The activation of hepatic stellate cells (HSCs) is a key event in fibrotic pathogenesis. However, the mechanism involving activation of HSCs in chronic schistosomiasis is not entirely clear. METHODS: Human HSC LX-2 and human umbilical vein endothelial cells (ECs) were cultured with Schistosoma japonicum (S. japonicum) antigens (SA) in vitro. Fibrosis-associated genes and cell proliferation were analyzed. HSCs were isolated from mice of chronic schistosomiasis with or without praziquantel (PZQ) treatment, followed by the microarray analysis for the liver fibrosis-associated pathways...
November 3, 2016: Immunology and Cell Biology
Wei-Ling Lin, Chia-Chi Chen, Guey-Yueh Shi, Chih-Yuan Ma, Chuan-Fa Chang, Hua-Lin Wu
The leukocyte adhesion cascade involves multiple events that efficiently localize circulating leukocytes into the injured sites to mediate inflammatory responses. From rolling to firm adhesion, the interactions between adhesion molecules play pivotal roles in increasing the avidity of leukocytes to endothelial cells. Thrombomodulin (TM), an essential anticoagulant protein in the vasculature, is also expressed on leukocytes. We previously demonstrated that Lewis(y) (Le(y)), a specific ligand of TM, is upregulated in inflamed endothelium and is involved in leukocyte adhesion...
November 3, 2016: Immunology and Cell Biology
Luís C Santos, David A Blair, Sudha Kumari, Michael Cammer, Thomas Iskratsch, Olivier Herbin, Konstantina Alexandropoulos, Michael L Dustin, Michael P Sheetz
The immunological synapse formed between a T-cell and an antigen-presenting cell is important for cell-cell communication during T-cell-mediated immune responses. Immunological synapse formation begins with stimulation of the T-cell receptor (TCR). TCR microclusters are assembled and transported to the center of the immunological synapse in an actin polymerization-dependent process. However, the physical link between TCR and actin remains elusive. Here we show that lymphocyte-specific Crk-associated substrate (Cas-L), a member of a force sensing protein family, is required for transport of TCR microclusters and for establishing synapse stability...
November 1, 2016: Immunology and Cell Biology
Scott A Budda, Krishna Bhattarai, Justine L Alexander, Lauren A Zenewicz
The cytokine interleukin-22 (IL-22) is a potent regulator of tissue responses during inflammation. Depending on the context of inflammation, IL-22 can have protective or inflammatory effects on epithelial cells. This dual-nature of IL-22 leads us to hypothesize that its activity must be exquisitely regulated in order to prevent host tissue damage. Environmental factors may act as a cellular cue as to how cells respond to IL-22. Inflammatory environments are characterized by low oxygen and thus we examined whether cells respond differently to IL-22 hypoxia compared to normoxia...
October 31, 2016: Immunology and Cell Biology
Ahmad Kotb, Antonina Klippert, Maria Daskalaki, Ulrike Sauermann, Christiane Stahl-Hennig, Berit Neumann
Granzyme B-expressing (GrB(+)) B cells are thought to contribute to immune dysfunctions in HIV patients, but so far their exact role is unknown. This report demonstrates for the first time the existence of GrB(+) B cells in SIV-infected rhesus macaques, which represent the most commonly used nonhuman primate model for HIV research. Similar to HIV patients, we found significantly higher frequencies of these cells in the blood of chronically SIV-infected rhesus monkeys compared with uninfected healthy ones. These frequencies correlated with plasma viral load and inversely with absolute CD4 T-cell counts...
October 25, 2016: Immunology and Cell Biology
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