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Journal of Leukocyte Biology

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https://www.readbyqxmd.com/read/28928269/perturbed-cd8-t-cell-immunity-across-universal-influenza-epitopes-in-the-elderly
#1
Thi H O Nguyen, Sneha Sant, Nicola L Bird, Emma J Grant, E Bridie Clemens, Marios Koutsakos, Sophie A Valkenburg, Stephanie Gras, Martha Lappas, Anthony Jaworowski, Jane Crowe, Liyen Loh, Katherine Kedzierska
Influenza epidemics lead to severe illness, life-threatening complications, and deaths, especially in the elderly. As CD8(+) T cells are associated with rapid recovery from influenza, we investigated the effects of aging on antigen-specific CD8(+) T cells across the universal influenza epitopes in humans. We show that aging is characterized by altered frequencies in T cell subsets, with naive T cells being partially replaced by activated effector/memory populations. Although we observed no striking differences in TCR signaling capacity, T cells in the elderly had increased expression of transcription factors Eomes and T-bet, and such changes were most apparent in CD8(+) T cells...
September 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28928268/mild-acidosis-delays-neutrophil-apoptosis-via-multiple-signaling-pathways-and-acts-in-concert-with-inflammatory-mediators
#2
Driss El Kebir, Everton de Oliveira Lima Dos Santos, Soukaina Mansouri, Meriem Sekheri, János G Filep
Accumulating evidence indicates development of local extracellular acidosis in inflamed tissues in response to infection and tissue injury. Activation of infiltrating neutrophils contributes to a transient decrease in pH, which, in turn, triggers innate immunity. In this study, we investigated the impact of extracellular acidosis on neutrophil apoptosis, a critical determinant of the outcome of the inflammatory response and analyzed the underlying signaling pathways. Culture of human isolated neutrophils in mildly acidotic conditions (pH 6...
September 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28899907/a-novel-function-of-cxcl10-in-mediating-monocyte-production-of-proinflammatory-cytokines
#3
Qihong Zhao, Taeg Kim, Jian Pang, Wendy Sun, Xiaoxia Yang, Jinhong Wang, Yunling Song, Hongwei Zhang, Huadong Sun, Vangipuram Rangan, Shrikant Deshpande, Huaping Tang, Mary Ellen Cvijic, Richard Westhouse, Timothy Olah, Jenny Xie, Mary Struthers, Luisa Salter-Cid
IFN-γ-inducible protein 10 (CXCL10), a chemokine that is abundantly secreted in response to inflammatory stimuli, has been implicated in the pathogenesis of multiple inflammatory diseases, such as inflammatory bowel disease. Whereas CXCL10 is traditionally recognized for recruiting pathogenic T cells to inflamed sites, its nonchemotactic role during inflammation remains poorly defined. In this report, we identified a novel function of CXCL10 in the regulation of the inflammatory potential of human monocytes to produce cytokines...
September 12, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28882904/frontline-science-proliferation-of-ly6c-monocytes-during-urinary-tract-infections-is-regulated-by-il-6-trans-signaling
#4
Akanksha Dixit, Jenny Bottek, Anna-Lena Beerlage, Jana Schuettpelz, Stephanie Thiebes, Alexandra Brenzel, Christoph Garbers, Stefan Rose-John, Hans-Willi Mittrücker, Anthony Squire, Daniel R Engel
Ly6C(+) monocytes are important components of the innate immune defense against infections. These cells have been shown to proliferate in the bone marrow of mice with systemic infections. However, the proliferative capacity of Ly6C(+) monocytes in infected peripheral tissues as well as the associated regulatory mechanisms remain unclear. In this study, we analyzed the proliferative capacity of Ly6C(+) monocytes in the urinary bladder after infection with uropathogenic E. coli, one of the most prevalent pathogen worldwide, and in LPS-induced peritonitis...
September 7, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28877954/suppression-of-toll-like-receptor-2-mediated-proinflammatory-responses-by-mycobacterium-tuberculosis-protein-rv3529c
#5
Upasana Bandyopadhyay, Attinder Chadha, Priya Gupta, Brijendra Tiwari, Kausik Bhattacharyya, Sonam Popli, Rajagopal Raman, Vani Brahamachari, Yogendra Singh, Pawan Malhotra, Krishnamurthy Natarajan
Microorganisms are known to devise various strategies to thwart protective responses by the host. One such strategy is to incorporate sequences and domains in their genes/proteins that have similarity to various domains of the host proteins. In this study, we report that Mycobacterium tuberculosis protein Rv3529c exhibits significant similarity to the death domain of the TLR pathway adaptor protein MyD88. Incubation of macrophages with Rv3529c specifically inhibited TLR2-mediated proinflammatory responses. This included attenuated oxidative burst, reduced phosphorylation of MAPK-ERK, reduced activation of transcription factor NF-κB and reduced secretion of proinflammatory cytokines IFN-γ, IL-6, and IL-17A with a concomitant increased secretion of suppressor cytokines IL-10 and TGF-β...
September 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28877953/anti-inflammatory-roles-of-p38%C3%AE-mapk-in-macrophages-are-context-dependent-and-require-il-10
#6
Abbas Raza, Jessica W Crothers, Mahalia M McGill, Gary M Mawe, Cory Teuscher, Dimitry N Krementsov
The p38 MAPK pathway was originally identified as a master regulator of proinflammatory cytokine production by myeloid cells. Numerous drugs targeting this kinase showed promise in preclinical models of inflammatory disease, but so far, none have shown efficacy in clinical trials. The reasons behind this are unclear, but may, in part, be explained by emerging anti-inflammatory functions of this kinase or overly refined selectivity of second-generation pharmacologic inhibitors. Here, we show that p38α signaling in macrophages plays pro- and anti-inflammatory functions in vivo and in vitro, with the outcome depending on the stimulus, output, kinetics, or mode of kinase inhibition (genetic vs...
September 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28864446/the-potential-of-the-microbiota-to-influence-vaccine-responses
#7
REVIEW
David J Lynn, Bali Pulendran
After clean water, vaccines are the primary public health intervention providing protection against serious infectious diseases. Antigen-specific antibody-mediated responses play a critical role in the protection conferred by vaccination; however these responses are highly variable among individuals. In addition, vaccine immunogenicity is frequently impaired in developing world populations, for reasons that are poorly understood. Although the factors that are associated with interindividual variation in vaccine responses are likely manifold, emerging evidence from mouse models and studies in human populations now suggests that the gut microbiome plays a key role in shaping systemic immune responses to both orally and parenterally administered vaccines...
September 1, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28855232/molecular-mechanisms-of-inflammasome-signaling
#8
REVIEW
Anukriti Mathur, Jenni A Hayward, Si Ming Man
The inflammasome is a macromolecular protein complex that mediates proteolytic cleavage of pro-IL-1β and -IL-18 and induces cell death in the form of pyroptosis. Certain nucleotide-binding oligomerization domain-like receptors (NLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), or tripartite motif (TRIM) family receptors trigger the assembly of an inflammasome in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Recent studies have revealed a multitude of host components and signals that are essential for controlling canonical and noncanonical inflammasome activation and pyroptosis...
August 30, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28851742/platelets-in-wiskott-aldrich-syndrome-victims-or-executioners
#9
REVIEW
Lucia Sereni, Maria Carmina Castiello, Anna Villa
Microthrombocytopenia is the clinical hallmark of WAS, a rare X-linked immunodeficiency that is characterized by eczema, autoimmunity, and cancer susceptibility. This disease is caused by mutations in the WAS gene, which is expressed in hematopoietic cells and regulates actin cytoskeleton remodeling thereby modulating various cellular functions, including motility, immunologic synapse assembly, and signaling. Despite extensive studies that have provided great insight into the relevance of this molecule to innate and cellular immunity, the exact mechanisms of microthrombocytopenia in WAS are still unknown...
August 29, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28848043/fatty-acid-synthase-regulates-the-pathogenicity-of-th17-cells
#10
Kathryne E Young, Stephanie Flaherty, Kaitlyn M Woodman, Neelam Sharma-Walia, Joseph M Reynolds
T cell activation and effector function is characterized by changes in metabolism. Altered metabolism is common to almost all types of activated T cells, but fatty acid synthesis seems to especially drive the formation of Th17 cells. Indeed, research has demonstrated that inhibition of early fatty acid synthesis through targeting of acetyl-CoA carboxylase (ACC1) can inhibit Th17 cell formation and instead promote the generation of regulatory T cells. Fatty acid synthase (FASN) is downstream of ACC, and previous studies have shown that FASN activity influences both cancer and inflammation...
August 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28848042/the-immunoinhibitory-pd-1-pd-l1-pathway-in-inflammatory-blood-vessel-disease
#11
Cornelia M Weyand, Gerald J Berry, Jörg J Goronzy
Because of their vital function, the wall structures of medium and large arteries are immunoprivileged and protected from inflammatory attack. That vascular immunoprivilege is broken in atherosclerosis and in vasculitis, when wall-invading T cells and macrophages (Mϕ) promote tissue injury and maladaptive repair. Historically, tissue-residing T cells were studied for their antigen specificity, but recent progress has refocused attention to antigen-nonspecific regulation, which determines tissue access, persistence, and functional differentiation of T cells...
August 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28848041/chemokines-encoded-by-herpesviruses
#12
REVIEW
Sergio M Pontejo, Philip M Murphy
Viruses use diverse strategies to elude the immune system, including copying and repurposing host cytokine and cytokine receptor genes. For herpesviruses, the chemokine system of chemotactic cytokines and receptors is a common source of copied genes. Here, we review the current state of knowledge about herpesvirus-encoded chemokines and discuss their possible roles in viral pathogenesis, as well as their clinical potential as novel anti-inflammatory agents or targets for new antiviral strategies.
August 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28821572/rolling-neutrophils-form-tethers-and-slings-under-physiologic-conditions-in-vivo
#13
Alex Marki, Konrad Buscher, Zbigniew Mikulski, Axel Pries, Klaus Ley
Human and mouse neutrophils are known to form tethers when rolling on selectins in vitro. Tethers are ∼0.2 μm thin, ∼5-10 μm-long structures behind rolling cells that can swing around to form slings that serve as self-adhesive substrates. Here, we developed a mouse intravital imaging method, where the neutrophil surface is labeled by injecting fluorescently labeled mAb to Ly-6G. Venules in the cremaster muscle of live mice were imaged at a high frame rate using a confocal microscope equipped with a fast resonant scanner...
August 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28811319/galectin-8-activates-dendritic-cells-and-stimulates-antigen-specific-immune-response-elicitation
#14
Julieta Carabelli, Valeria Quattrocchi, Alejandra D'Antuono, Patricia Zamorano, María Virginia Tribulatti, Oscar Campetella
Galectin-8 (Gal-8) is a mammalian β-galactoside-binding lectin, endowed with proinflammatory properties. Given its capacity to enhance antigen-specific immune responses in vivo, we investigated whether Gal-8 was also able to promote APC activation to sustain T cell activation after priming. Both endogenous [dendritic cells (DCs)] and bone marrow-derived DCs (BMDCs) treated with exogenous Gal-8 exhibited a mature phenotype characterized by increased MHC class II (MHCII), CD80, and CD86 surface expression. Moreover, Gal-8-treated BMDCs (Gal-8-BMDCs) stimulated antigen-specific T cells more efficiently than immature BMDCs (iBMDCs)...
August 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28807929/human-mucosal-associated-invariant-t-mait-cells-possess-capacity-for-b-cell-help
#15
Michael S Bennett, Shubhanshi Trivedi, Anita S Iyer, J Scott Hale, Daniel T Leung
Mucosal-associated invariant T (MAIT) cells are an innate-like T-cell subset, restricted by the nonclassic MHC class I-related protein MR1 and enriched at mucosal sites. Human studies have shown an association between MAIT cells and pathogen-specific antibody responses. In this study, we investigate the effect of human MAIT cells on B cells ex vivo. We found that supernatants from microbe- or cytokine-stimulated MAIT cells, when added to purified autologous B cells, increase frequencies of plasmablasts and promote IgA, IgG, and IgM production...
August 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28801344/frontline-science-macrophage-derived-exosomes-promote-neutrophil-necroptosis-following-hemorrhagic-shock
#16
Yang Jiao, Zhigang Li, Patricia A Loughran, Erica K Fan, Melanie J Scott, Yuehua Li, Timothy R Billiar, Mark A Wilson, Xueyin Shi, Jie Fan
Hemorrhagic shock (HS) renders patients susceptible to development of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) through mechanisms that are, as yet, unclear. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that controls cell release of inflammatory mediators from innate immune cells, such as polymorphonuclear neutrophils (PMNs), and critically regulates the progress of inflammation. In this study, we investigated the mechanisms of alveolar macrophage (AMϕ) effects on PMN necroptosis following HS...
August 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28798145/tnf-induces-neutrophil-adhesion-via-formin-dependent-cytoskeletal-reorganization-and-activation-of-%C3%AE-integrin-function
#17
Angélica Aparecida Antoniellis Silveira, Venina Marcela Dominical, Camila Bononi Almeida, Hanan Chweih, Wilson Alves Ferreira, Cristina Pontes Vicente, Fabio Trindade Maranhão Costa, Claudio C Werneck, Fernando Ferreira Costa, Nicola Conran
Although essential for inflammatory responses, leukocyte recruitment to blood vessel walls in response to inflammatory stimuli, such as TNF-α, can contribute to vascular occlusion in inflammatory diseases, including atherosclerosis. We aimed to further characterize the mechanisms by which TNF stimulates adhesive and morphologic alterations in neutrophils. Microfluidic and intravital assays confirmed the potent effect that TNF has on human and murine neutrophil adhesion and recruitment in vitro and in vivo, respectively...
August 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28798144/frontline-science-leishmania-mexicana-amastigotes-can-replicate-within-neutrophils
#18
Benjamin P Hurrell, Manon Beaumann, Sandrina Heyde, Ivo B Regli, Andreas J Müller, Fabienne Tacchini-Cottier
Cutaneous leishmaniasis is a neglected tropical disease, causing a spectrum of clinical manifestations varying from self-healing to unhealing lesions that may be very difficult to treat. Emerging evidence points to a detrimental role for neutrophils during the first hours following infection with many distinct Leishmania species (spp.) at a time when the parasite is in its nonreplicative promastigote form. Neutrophils have also been detected at later stages of infection in unhealing chronic cutaneous lesions...
August 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28768708/identification-of-compounds-that-decrease-numbers-of-mycobacteria-in-human-macrophages-in-the-presence-of-serum-amyloid-p
#19
Wang Xiang, Nehemiah Cox, Richard H Gomer
Mϕs are a heterogeneous population of cells and include classically activated Mϕs (M1) and alternatively activated Mϕs (M2). Mϕs can change from M1 to M2 and vice versa in response to environmental stimuli. Serum amyloid P (SAP) is a constitutive plasma protein that polarizes Mϕs to an M2 phenotype, and part of this effect is mediated through FcγRI receptors. In an effort to find ways to alter Mϕs phenotypes, we screened for compounds that can block the SAP-FcγRI interaction. From a screen of 3000 compounds, we found 12 compounds that reduced the ability of fluorescently labeled human SAP to bind cells expressing human FcγRI...
August 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28760822/reactivation-of-g%C3%AE-i-coupled-formyl-peptide-receptors-is-inhibited-by-g%C3%AE-q-selective-inhibitors-when-induced-by-signals-generated-by-the-platelet-activating-factor-receptor
#20
André Holdfeldt, Agnes Dahlstrand Rudin, Michael Gabl, Zahra Rajabkhani, Gabriele M König, Evi Kostenis, Claes Dahlgren, Huamei Forsman
Formyl peptide receptor (FPR)-desensitized neutrophils display increased production/release of superoxide (O2(-)) when activated by platelet-activating factor (PAF), a priming of the response achieved through a unique receptor crosstalk mechanism. The aim of this study was to determine the effect of an inhibitor selective for small, heterotrimeric G proteins belonging to the Gαq subclass on that receptor crosstalk. We show that signals generated by FPRs and the PAF receptor (PAFR) induce activation of the neutrophil O2(-), producing NADPH-oxidase, and that response was sensitive to Gαq inhibition in cells activated by PAF, but no inhibition was obtained in cells activated by FPR agonists...
July 31, 2017: Journal of Leukocyte Biology
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