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Mitra Bhattacharyya, James B Whitney, Michael Seaman, Dan H Barouch, Pablo Penaloza-MacMaster
Antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV) infection represents a major breakthrough in the treatment of HIV/AIDS. However, it remains unclear how ART influences virus-specific immune responses. Understanding how ART influences virus-specific immune responses is important for developing novel cure and eradication interventions for HIV-1. In the present study, we evaluate how ART impacts T cell and antibody responses in simian immunodeficiency virus (SIV) infected rhesus macaques...
July 17, 2018: Immunology
Sandeep Kumar Dhanda, Kerrie Vaughan, Veronique Schulten, Alba Grifoni, Daniela Weiskopf, John Sidney, Bjoern Peters, Alessandro Sette
Epitopes identified in large-scale screens of overlapping peptides often share significant levels of sequence homology, complicating the analysis of epitope-related data. Clustering algorithms are often used to facilitate these analyses, but available methods are generally insufficient in their capacity to define biologically meaningful epitope clusters in the context of the immune response. To fulfill this need we developed an algorithm that generates epitope clusters based on representative or consensus sequences...
July 17, 2018: Immunology
Min Yang, Katrin Klocke, Clara Marquina Hernandez, Bingze Xu, Inger Gjertsson, Kajsa Wing, Rikard Holmdahl
CD4+ Foxp3+ regulatory T cells (Tregs) can control both cellular and humoral immune responses, however, when and how Tregs play a predominant role in regulating autoimmune disease remains elusive. To deplete Tregs in vivo at given time points, we used a mouse strain, susceptible to glucose-6-phosphate isomerase peptide induced arthritis (GIA), in which the deletion of Tregs can be controlled by diphtheria toxin treatment. By depleting Tregs in GIA mouse model, we found that a temporary lack of Tregs at both priming and onset exaggerated disease development...
July 10, 2018: Immunology
Wioleta M Zelek, Matthew Stott, David Walters, Claire L Harris, B Paul Morgan
C5 plays a major role in complement activation; C5 convertase cleaves C5 into the pro-inflammatory C5a, and C5b, the nidus for formation of the lytic membrane attack complex (MAC). C5 is a major target for anti-complement drugs, necessitating better methods for study of C5 function. Purification of C5 is complicated; classical methods involve precipitation or pH shifts that result in functional loss and low yield. We here present a method for C5 purification utilising a novel anti-C5 monoclonal antibody (mAb); RO7112689 (C5i mAb, SKY59), pH-switch engineered to induce antibody-antigen dissociation in the acidic endosome (~pH5...
July 7, 2018: Immunology
Hang Zhao, Yating Ma, Leifang Zhang
Although low molecule mass hyaluronan (LMMHA) has been implicated in pulmonary inflammatory diseases, the signaling pathway of LMMHA (200 kDa) that initiates the inflammatory response in lung is still unknown. In this study, we evaluate the role of PI3K and its downstream signaling pathway in LMMHA-induced lung inflammatory responses. Our results indicate that pharmacological inhibition of PI3K or genetic deletion of Akt1 enhances neutrophil apoptosis, attenuates neutrophils influx into the lungs of mice and diminishes the expression of pro-inflammatory factors such as IL-6, keratinocyte cell-derived chemokine (KC) and pro-matrix metalloproteinases-9 (MMP-9) in bronchoalveolar lavage fluid (BALF) after intratracheal administration of LMMHA...
July 5, 2018: Immunology
Julieta Carabelli, Cecilia Arahí Prato, Liliana María Sanmarco, Maria Pilar Aoki, Oscar Campetella, María Virginia Tribulatti
Galectin-8 (Gal-8) is a mammalian lectin endowed with the ability to costimulate antigen-specific immune responses. We have previously demonstrated that bone marrow-derived dendritic cells produce high levels of IL-6 in response to Gal-8 stimulation. Since IL-6 is a pleiotropic cytokine that has a broad effect on cells of the immune system, in the present study we aimed to elucidate whether IL-6 was involved in Gal-8-dependent costimulatory signals during antigen recognition by specific CD4 T cells. To this aim, splenocytes from DO11...
July 4, 2018: Immunology
Magalí C Girard, Gonzalo R Acevedo, Lucía López, Micaela S Ossowski, María D Piñeyro, Juan P Grosso, Marisa Fernandez, Yolanda Hernández Vasquez, Carlos Robello, Karina A Gómez
Trypanosoma cruzi, the etiological agent of Chagas disease, has a highly efficient detoxification system to deal with the oxidative burst imposed by its host. One of the antioxidant enzymes involved is the cytosolic tryparedoxin peroxidase (c-TXNPx) which catalyzes the reduction of hydrogen peroxide, small-chain organic hydroperoxides and peroxynitrite. This enzyme is present in all parasite stages, and its over-expression renders parasites more resistant to oxidative defenses of macrophages, favoring parasite survival...
July 4, 2018: Immunology
Felix Clemens Richter, Sandrine Obba, Anna Katharina Simon
Immune cell differentiation and function depend on metabolic changes for the provision of energy and metabolites. Consequently, cellular metabolism relies on the availability of micronutrients such as vitamins and energy-rich sources including amino acids and fatty acids. The bone marrow controls the continuous production of blood cells and is thereby reliant on the sophisticated interplay of progenitor and mature immune cells with its stromal microenvironment. The significance of stromal subsets in immunopoiesis is undisputed, however our current knowledge is limited to their role in the production and secretion of a variety of soluble proteins such as cytokines...
July 4, 2018: Immunology
Zhiming Wang, Hushan Zhang, Ronghua Liu, Tingting Qian, Jiajing Liu, Enyu Huang, Zhou Lu, Chujun Zhao, Luman Wang, Yiwei Chu
Regulatory T cells (Tregs) play an essential role in the maintenance of intestinal homeostasis. In Peyer's Patches (PPs), which comprise the most important IgA induction site in the gut-associated lymphoid tissue, Tregs promote IgA isotype switching. However, the mechanisms underlying their entry into PPs and isotype switching facilitation in activated B cells remains unknown. This study, based on the dextran sulfate sodium (DSS)-induced colitis model, revealed that Tregs are significantly increased in PPs, along with CD11b+ B cell induction...
July 3, 2018: Immunology
Luca Cassetta, Takanori Kitamura
Tumour-infiltrating immune cells regulate the tumour development and progression either negatively or positively. For example, cytotoxic lymphocytes (CTL) such as CD8+ T and natural killer (NK) cells can recognize and eliminate cancer cells, and thereby restrict the tumour growth and metastasis, if they exert full cytotoxicity. In contrast, tumour-infiltrating myeloid cells such as tumour-associated macrophages (TAM) promote the expansion and dissemination of cancer cells depending on their functional states...
July 2, 2018: Immunology
Julian R Marchesi
No abstract text is available yet for this article.
June 25, 2018: Immunology
Mark R Griffiths, Marina Botto, B Paul Morgan, J W Neal, P Gasque
Microglia and non-professional immune cells (endothelial cells, neurons) participate in the recognition and removal of pathogens and tissue-debris in the injured CNS through major pro-inflammatory processes. However, the mechanisms involved in regulating these responses remain ill-characterised. We herein show that CD93 also known as complement C1qRp/AA4 stem cell marker has an important role in the regulation of inflammatory processes. The role of CD93 was evaluated in two models of neuroinflammation. We used the MOG-experimental autoimmune encephalomyelitis (EAE) model and the antibody-dependent EAE (ADEAE) which were induced in wild type and CD93 knockout mice...
June 20, 2018: Immunology
Ismail Sebina, Ashraful Haque
Type I interferons (IFNs) are a family of cytokines with a wide range of biological activities including anti-viral and immune-regulatory functions. Here, we focus on the protozoan parasitic disease malaria, and examine the effects of type I IFN-signalling during Plasmodium infection of humans and experimental mice. Since the 1960s, there have been many studies in this area, but a simple explanation for the role of type I IFN has not emerged. Although epidemiological data are consistent with roles for type I IFN in influencing malaria disease severity, functional proof of this remains sparse in humans...
June 16, 2018: Immunology
Hannah Tomlin, Anna M Piccinini
The role of the host extracellular matrix (ECM) in infection tends to be neglected. However, the complex interactions between invading pathogens, host tissues and immune cells occur in the context of the ECM. On the pathogen side, a variety of surface and secreted molecules, including microbial surface components recognizing adhesive matrix molecules and tissue-degrading enzymes, are employed that interact with different ECM proteins to effectively establish an infection at specific sites. Microbial pathogens can also hijack or misuse host proteolytic systems to modify the ECM, evade immune responses or process biologically active molecules such as cell surface receptors and cytokines that direct cell behaviour and immune defence...
June 16, 2018: Immunology
Fatma Zehra Hapil, Gerhard Wingender
The surface of mammalian bodies is colonized by a multitude of microbial organisms, which under normal conditions support the host and are considered beneficial commensals. This requires, however, that the composition of the commensal microbiota is tightly controlled and regulated. The host immune system plays an important role in the maintenance of this microbiota composition. Here we focus on the contribution of one particular immune cell type, invariant Natural Killer T (iNKT) cells, in this process. The iNKT cells are a unique subset of T cells characterized by two main features...
June 12, 2018: Immunology
Ruihua Li, Ju Liu, Shipo Wu, Xiaodong Zai, Yaohui Li, Qiaoling Yang, Lihua Hou, Junjie Xu, Wei Chen
Adenoviral vectors (AdV) are considered promising candidates for vaccine applications. A prominent group of Toll-like receptors (TLRs) participate in the adenovirus-induced adaptive immune response, yet there is little information regarding the role of TLR4 in AdV-induced immune responses in recent literature. We investigated the function of TLR4 in both adaptive and innate immune responses to an AdV-based anthrax vaccine. By immunizing wild-type and TLR4 knockout (TLR4-KO) mice, we revealed the requirement of TLR4 in AdV-induced innate responses...
June 7, 2018: Immunology
Huanling Zhang, Yanyan Li, Xiaoping Liu, Zhaoduan Liang, Mengyong Yan, Qiang Liu, Anan Chen, Yifeng Bao, Chengzhi Zhou, Shiyue Li, Cassian Yee, Yi Li
Recently, bi-functional molecules that can redirect immune effectors to tumour cells have emerged as potentially robust mediators of tumour regression in clinical trials. Two modalities in particular, bi-specific antibodies for T-cell redirection and activation (BiTe) and immune-mobilizing monoclonal T-cell receptors against cancer (ImmTAC), are being evaluated in efficacy studies as 'off-the-shelf' reagents. Optimal therapy will require an understanding and means to address regulatory mechanisms of limiting efficacy...
May 23, 2018: Immunology
Andrew J McDermott, Bruce S Klein
The mucosal surface of the respiratory tract encounters microbes, such as fungal particles, with every inhaled breath. When pathogenic fungi breach the physical barrier and innate immune system within the lung to establish an infection, adaptive immunity is engaged, often in the form of helper CD4 T-cell responses. Type 1 responses, characterized by interferon-γ production from CD4 cells, promote clearance of Histoplasma capsulatum and Cryptococcus neoformans infection. Likewise, interleukin-17A (IL-17A) production from Th17 cells promotes immunity to Blastomyces dermatitidis and Coccidioides species infection by recruiting neutrophils...
May 20, 2018: Immunology
Lee I Garner, Andrew Hartland, Johannes Breuning, Marion H Brown
CD6 is a type I T-cell surface receptor that modulates antigen receptor signalling. Its activity is regulated by binding of its membrane proximal domain (domain 3) to a cell surface ligand, CD166. CD6 monoclonal antibodies (mAbs) specific for the membrane distal domain (domain 1) perturb CD6 function including itolizumab (Alzumab™), which has reached the clinic for treatment of autoimmune disease. We characterized molecular and functional properties of several CD6 mAbs including itolizumab to define potential mechanisms of action...
May 17, 2018: Immunology
Muzamil Y Want, Amit A Lugade, Sebastiano Battaglia, Kunle Odunsi
Major progress in the analysis of human immune responses to cancer has been made through the molecular characterization of human tumour antigens. The development of therapeutic strategies for eliciting immune-mediated rejection of tumours has accelerated due to the elucidation of the molecular basis for tumour cell recognition and destruction by immune cells. Of the various human tumour antigens defined to date in ovarian cancer, the cancer-testis (CT) family of antigens have been studied extensively preclinically and clinically because of their testis-restricted expression in normal tissues and ability to elicit robust immune responses...
May 17, 2018: Immunology
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