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European Journal of Immunology

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https://www.readbyqxmd.com/read/28805251/wiskott-aldrich-syndrome-protein-emerging-mechanisms-in-immunity
#1
REVIEW
Elizabeth Rivers, Adrian J Thrasher
The Wiskott Aldrich syndrome protein (WASP) participates in innate and adaptive immunity through regulation of actin cytoskeleton-dependent cellular processes, including immune synapse formation, cell signaling, migration and cytokine release. There is also emerging evidence for a direct role in nuclear transcription programmes uncoupled from actin polymerization. A deeper understanding of some of the more complex features of Wiskott Aldrich syndrome (WAS) itself, such as the associated autoimmunity and inflammation, has come from identification of defects in the number and function of anti-inflammatory myeloid cells and regulatory T and B cells, as well as defects in positive and negative B-cell selection...
August 14, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28799230/human-dendritic-cells-activated-with-mv130-induce-th1-th17-and-il-10-responses-via-ripk2-and-myd88-signalling-pathways
#2
Cristina Cirauqui, Cristina Benito-Villalvilla, Silvia Sánchez-Ramón, Sofía Sirvent, Carmen M Diez-Rivero, Laura Conejero, Paola Brandi, Lourdes Hernández-Cillero, Juliana Lucía Ochoa, Beatriz Pérez-Villamil, David Sancho, José Luis Subiza, Oscar Palomares
Recurrent respiratory tract infections (RRTIs) are the first leading cause of community- and nosocomial-acquired infections. Antibiotics remain the mainstay of treatment, enhancing the potential to develop antibiotic resistances. Therefore, the development of new alternative approaches to prevent and treat RRTIs is highly demanded. Daily sublingual administration of the whole heat-inactivated polybacterial preparation (PBP) MV130 significantly reduced the rate of respiratory infections in RRTIs patients, however, the immunological mechanisms of action remain unknown...
August 11, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28776644/glucocorticoids-downregulate-tlr4-signaling-activity-via-its-direct-targeting-by-mir-511-5p
#3
Graziella Curtale, Tiziana A Renzi, Lorenzo Drufuca, Marcello Rubino, Massimo Locati
Endotoxin tolerance assures proper regulation of the TLR4 signaling pathway and avoids uncontrolled inflammation, limiting tissue damage and endotoxin shock development. Though underlying molecular mechanisms are still undefined, evidence indicates the involvement of microRNAs, which represent a new layer of regulation of inflammatory pathways. Here we report that LPS and other inflammatory stimuli repress miR-511-5p expression in human monocytes, while anti-inflammatory stimuli, such as TGFβ and glucocorticoids, have the opposite effect...
August 4, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28776643/contributions-of-the-intestinal-microbiome-in-lung-immunity
#4
REVIEW
Jeremy P McAleer, Jay K Kolls
The intestine is a critical site of immune cell development that not only controls intestinal immunity but extra-intestinal immunity as well. Recent findings have highlighted important roles for gut microbiota in shaping lung inflammation. Here, we discuss interactions between the microbiota and immune system including T cells, protective effects of microbiota on lung infections, the role of diet in shaping the composition of gut microbiota and susceptibility to asthma, epidemiologic evidence implicating antibiotic use and microbiota in asthma and clinical trials investigating probiotics as potential treatments for atopy and asthma...
August 4, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28771693/herpes-simplex-virus-1-interferes-with-autophagy-of-murine-dendritic-cells-and-impairs-their-ability-to-stimulate-cd8-t-lymphocytes
#5
Ramachandramouli Budida, Metodi V Stankov, Katinka Döhner, Anna Buch, Diana Panayotova-Dimitrova, Kim A Tappe, Anja Pohlmann, Beate Sodeik, Georg M N Behrens
The MHC class I presentation is responsible for the presentation of viral proteins to CD8(+) T lymphocytes and mainly depends on the classical antigen processing pathway. Recently, a second pathway involving autophagy has been implicated in this process. Here, we show an increase in the capacity of murine dendritic cells to present viral antigens on MHC class I after infection with a mutant herpes simplex virus 1 (HSV-1-Δ34.5), lacking ICP34.5, when compared to its parental HSV-1 strain. The ICP34.5 protein counteracts host cell translational arrest and suppresses macroautophagy, and the lack of this protein resulted in a low viral protein abundance, which was processed and presented in an efficient way...
August 3, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28771702/igg-subclass-and-vaccination-stimulus-determine-changes-in-antigen-specific-antibody-glycosylation-in-mice
#6
Daniela Kao, Anja Lux, Anja Schaffert, Roland Lang, Friedrich Altmann, Falk Nimmerjahn
Immunoglobulin G (IgG) glycosylation can modulate antibody effector functions. Depending on the precise composition of the sugar moiety attached to individual IgG glycovariants either pro- or anti-inflammatory effector pathways can be initiated via differential binding to type I or type II Fc-receptors. However, an in depth understanding of how individual IgG subclasses are glycosylated during the steady state and how their glycosylation pattern changes during vaccination is missing. To monitor IgG subclass glycosylation during the steady state and upon vaccination of mice with different T cell dependent and independent antigens, tryptic digests of serum and antigen specific IgG preparations were analysed by reversed phase-liquid chromatography-mass spectrometry...
August 2, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28762530/high-proportion-of-pd-1-expressing-cd4-t-cells-in-adipose-tissue-constitutes-an-immunomodulatory-microenvironment-that-may-support-hiv-persistence
#7
Abderaouf Damouche, Guillaume Pourcher, Valérie Pourcher, Stéphane Benoist, Elodie Busson, Jean Jacques Lataillade, Mélanie Le Van, Thierry Lazure, Julien Adam, Benoit Favier, Bruno Vaslin, Michaela Müller-Trutwin, Olivier Lambotte, Christine Bourgeois
We and others have demonstrated that adipose tissue is a reservoir for HIV. Evaluation of the mechanisms responsible for viral persistence may lead to ways of reducing these reservoirs. Here, we evaluated the immune characteristics of adipose tissue in HIV-infected patients receiving antiretroviral therapy (ART) and in non-HIV-infected patients. We notably sought to determine whether adipose tissue's intrinsic properties and/or HIV induced alteration of the tissue environment may favour viral persistence. ART-controlled HIV infection was associated with a difference in the CD4/CD8 T-cell ratio and an elevated proportion of Treg cells in subcutaneous adipose tissue...
August 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28762497/t-cell-dependent-antigen-adjuvanted-with-dotap-cpg-b-but-not-dotap-cpg-a-induces-robust-germinal-center-responses-and-high-affinity-antibodies-in-mice
#8
Munir Akkaya, Billur Akkaya, Patrick W Sheehan, Pietro Miozzo, Mirna Pena, Chen-Feng Qi, Javier Manzella-Lapeira, Silvia Bolland, Susan K Pierce
The development of vaccines for infectious diseases for which we currently have none, including HIV, will likely require the use of adjuvants that strongly promote germinal center responses and somatic hypermutation to produce broadly neutralizing antibodies. Here we compared the outcome of immunization with the T-cell dependent antigen, NP-conjugated to chicken gamma globulin (NP-CGG) adjuvanted with the toll-like receptor 9 (TLR9) ligands, CpG-A or CpG-B, alone or conjugated with the cationic lipid carrier, DOTAP...
August 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28762472/absence-of-notch1-in-murine-myeloid-cells-attenuates-the-development-of-experimental-autoimmune-encephalomyelitis-by-affecting-th1-and-th17-priming
#9
Miriam Fernández, Eva M Monsalve, Susana López-López, Almudena Ruiz-García, Susana Mellado, Elena Caminos, José Javier García-Ramírez, Jorge Laborda, Pedro Tranque, María José M Díaz-Guerra
Inhibition of Notch signalling in T cells attenuates the development of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Growing evidence indicates that myeloid cells are also key players in autoimmune processes. Thus, the present study evaluates the role of the Notch1 receptor in myeloid cells on the progression of myelin oligodendrocyte glycoprotein (MOG)35-55 -induced EAE, using mice with a myeloid-specific deletion of the Notch1 gene (MyeNotch1KO). We found that EAE progression was less severe in the absence of Notch1 in myeloid cells...
August 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28748529/dual-role-of-monocyte-derived-dendritic-cells-in-trypanosoma-cruzi-infection
#10
Carolina V Poncini, Stella M González-Cappa
Pathogens can cause inflammation when inoculated into the skin. The vector-transmitted protozoan parasite Trypanosoma cruzi induces poor cellular-infiltration and disseminates, causing high mortality in the experimental model. Here, we characterized the inflammatory foci at the parasite inoculation site and secondary lymphoid organs using a murine system. While no macrophages and few neutrophils and monocytes (Mo) were recruited into the skin, T. cruzi infection elicited the mobilization of Ly6C(+) Mo to draining lymph nodes and spleen...
July 27, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28744851/post-translational-regulation-of-antiviral-innate-signaling
#11
REVIEW
Yilong Zhou, Chenxi He, Wang Lin, Baoxue Ge
The innate immune system initiates immune responses by pattern-recognition receptors (PRR). Virus-derived nucleic acids are sensed by the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family and the toll-like receptor (TLR) family as well as the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). These receptors activate IRF3/7 and NF-κB signaling pathways to induce the expression of type I interferons (IFNs) and other cytokines firing antiviral responses within the cell. However, to achieve a favorable outcome for the host, a balanced production of IFNs and activation of antiviral responses is required...
July 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28742217/the-inflammatory-cytokine-interferon-gamma-inhibits-sortilin-1-expression-in-hepatocytes-via-the-jak-stat-pathway
#12
John Pirault, Konstantinos A Polyzos, Marcelo H Petri, Daniel Fj Ketelhuth, Magnus Bäck, Göran K Hansson
Sortilin-1, a receptor of the VPS10p family, has been associated with cardiovascular disease in genome-wide association studies. It is implicated in lipoprotein metabolism, secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) and secretion of inflammatory cytokines. However, its own regulation remains unclear. Chronic inflammation is a hallmark of atherosclerosis and absence of regulatory T (Treg) cells is associated with reduced protein expression of sortilin-1 in the liver. Therefore, we postulated that mediator(s) of inflammation known to be downregulated by regulatory T cells may modulate sortilin-1 expression...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28741728/ebi2-contributes-to-the-induction-of-thymic-central-tolerance-in-mice-by-promoting-rapid-motility-of-medullary-thymocytes
#13
Sanghee Ki, Hiran M Thyagarajan, Zicheng Hu, Jessica N Lancaster, Lauren I R Ehrlich
Maturing thymocytes enter the thymic medulla, where they encounter numerous self-antigens presented by antigen presenting cells (APCs). Those thymocytes that are strongly self-reactive undergo either negative selection or diversion into the regulatory T cell lineage. Although the majority of the proteome is expressed in the medulla, many self-antigens are expressed by only a minor fraction of medullary APCs; thus, thymocytes must efficiently enter the medulla and scan APCs to ensure central tolerance. Chemokine receptors promote lymphocyte migration, organization within tissues, and interactions with APCs in lymphoid organs...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28741710/il-33-expanded-human-v%C3%AE-9v%C3%AE-2-t-cells-have-anti-lymphoma-effect-in-a-mouse-tumor-model
#14
Caroline Duault, Delphine Betous, Christine Bezombes, Stéphane Roga, Corinne Cayrol, Jean-Philippe Girard, Jean-Jacques Fournié, Mary Poupot
From several years, the anticancer effects of Vγ9 T lymphocytes make these cells good candidates for cancer immunotherapies. However, the proved efficacy of γδ Τ cell-based cancer immunotherapies in some clinical trials was minimized due to the inherent toxicity of IL-2, which is essential for the combination therapy with Phosphoantigen (PAg). Recently, we showed that IL-33, a γ chain receptor-independent cytokine, was able to induce the in vitro proliferation of PAg-activated Vγ9 T cells, which were fully functional expressing IFN-γ and TNF-α and showing in vitro anti-tumor cytotoxicity...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28741316/role-of-cd4-t-cell-helper-subsets-in-immune-response-and-deviation-of-cd8-t-cells-in-mice
#15
Alison Hogg, Yongjun Sui, Shlomo Z Ben-Sasson, William E Paul, Jay A Berzofsky
The ability of different CD4(+) T cell subsets to help CD8(+) T-cell response is not fully understood. Here, we found using the murine system that Th17 cells induced by IL-1β, unlike Th1, were not effective helpers for antiviral CD8 responses as measured by IFNγ-producing cells or protection against virus infection. However, they skewed CD8 responses to a Tc17 phenotype. Thus, the apparent lack of help was actually immune deviation. This skewing depended on both IL-21 and IL-23. To overcome this effect, we inhibited Th17 induction by blocking TGF-β...
July 24, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28736941/in-vivo-neutralization-of-%C3%AE-4-and-%C3%AE-7-integrins-inhibits-eosinophil-trafficking-and-prevents-lung-injury-during-tropical-pulmonary-eosinophilia-in-mice
#16
Pankaj Sharma, Aditi Sharma, Mrigank Srivastava
Integrins regulate leukocyte trafficking during homeostasis and inflammatory conditions. However, the role of α4 and β7 integrins in guiding eosinophil transmigration into the lungs during filarial manifestation of Tropical Pulmonary Eosinophilia (TPE) has not been explored. In this study, mice exhibiting TPE manifestations were administered with in vivo neutralizing antibodies against integrins α4 and β7 or their combination and immuno-pathological parameters were evaluated. Results show an intact lung barrier, significantly lower lung inflammation and reduced eosinophil counts in the Bronchoalveolar lavage fluid and lungs of mice receiving anti-α4(+) β7 treatment...
July 24, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28736835/peptide-mimetics-of-immunoglobulin-a-iga-and-fc%C3%AE-ri-block-iga-induced-human-neutrophil-activation-and-migration
#17
Marieke H Heineke, Lydia P E van der Steen, Rianne M Korthouwer, J Joris Hage, Johannes P M Langedijk, Joris J Benschop, Jantine E Bakema, Jerry W Slootstra, Marjolein van Egmond
The cross-linking of the IgA Fc receptor (FcαRI) by IgA induces release of the chemoattractant LTB4, thereby recruiting neutrophils in a positive feedback loop. IgA autoantibodies of patients with autoimmune blistering skin diseases therefore induce massive recruitment of neutrophils, resulting in severe tissue damage. To interfere with neutrophil mobilization and reduce disease morbidity, we developed a panel of specific peptides mimicking either IgA or FcαRI sequences. CLIPS technology was used to stabilize three-dimensional structures and to increase peptides' half-life...
July 24, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28718914/reduced-numbers-of-circulating-group-2-innate-lymphoid-cells-in-patients-with-common-variable-immunodeficiency
#18
Christoph B Geier, Sophie Kraupp, David Bra, Martha M Eibl, Jocelyn R Farmer, Krisztian Csomos, Jolan E Walter, Hermann M Wolf
Recent studies identified an emerging role of group 2 and 3 innate lymphoid cells (ILCs) as key players in the generation of T-dependent and T-independent antibody production. In this retrospective case-control study CD117(+) ILCs (including the majority of ILC2 and ILC3) were reduced in patients with common variable immunodeficiency (CVID). The reduction in CD117(+) ILCs was distinctive to CVID and could not be observed in patients with X linked agammaglobulinemia (XLA). Patients with a more pronounced reduction in CD117(+) ILC numbers showed significantly lower numbers of peripheral MZ-like B cells and an increased prevalence of chronic, non-infectious enteropathy...
July 18, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28691750/human-neonatal-thymectomy-induces-altered-b-cell-responses-and-auto-reactivity
#19
Theo Broek, Asaf Madi, Eveline M Delemarre, Alvin W L Schadenberg, Kiki Tesselaar, José A M Borghans, Stefan Nierkens, Frank A Redegeld, Henny G Otten, Maura Rosetti, Salvatore Albani, Rachel Sorek, Irun R Cohen, Nicolaas J G Jansen, Femke van Wijk
An association between T-cell lymphopenia and autoimmunity has long been proposed, but it remains to be elucidated whether T-cell lymphopenia affects B-cell responses to auto-antigens. Human neonatal thymectomy results in a decrease in T-cell numbers and we used this model to study the development of auto-reactivity. Two cohorts of neonatally thymectomized individuals were examined, a cohort of young (1-5 years post-thymectomy, n = 10-27) and older children (>10years,n = 26), and compared to healthy age-matched controls...
July 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28688208/human-profilin-1-is-a-negative-regulator-of-ctl-mediated-cell-killing-and-migration
#20
Rouven Schoppmeyer, Renping Zhao, He Cheng, Mohamed Hamed, Chen Liu, Xiao Zhou, Eva C Schwarz, Yan Zhou, Arne Knörck, Gertrud Schwär, Shunrong Ji, Liang Liu, Jiang Long, Volkhard Helms, Markus Hoth, Xianjun Yu, Bin Qu
The actin-binding protein profilin1 (PFN1) plays a central role in actin dynamics, which is essential for cytotoxic T lymphocyte (CTL) functions. The functional role of PFN1 in CTLs, however still remains elusive. Here, we identify PFN1 as the only member of the profilin family expressed in primary human CD8(+) T cells. Using in vitro assays, we find that PFN1 is a negative regulator of CTL-mediated elimination of target cells. Furthermore, PFN1 is involved in activation-induced lytic granule (LG) release, CTL migration and modulation of actin structures at the immunological synapse (IS)...
July 8, 2017: European Journal of Immunology
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