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Immunopathology

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https://www.readbyqxmd.com/read/28228281/dysregulation-of-the-cytokine-gm-csf-induces-spontaneous-phagocyte-invasion-and-immunopathology-in-the-central-nervous-system
#1
Sabine Spath, Juliana Komuczki, Mario Hermann, Pawel Pelczar, Florian Mair, Bettina Schreiner, Burkhard Becher
Chronic inflammatory diseases are influenced by dysregulation of cytokines. Among them, granulocyte macrophage colony stimulating factor (GM-CSF) is crucial for the pathogenic function of T cells in preclinical models of autoimmunity. To study the impact of dysregulated GM-CSF expression in vivo, we generated a transgenic mouse line allowing the induction of GM-CSF expression in mature, peripheral helper T (Th) cells. Antigen-independent GM-CSF release led to the invasion of inflammatory myeloid cells into the central nervous system (CNS), which was accompanied by the spontaneous development of severe neurological deficits...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228272/commanding-cns-invasion-gm-csf
#2
Junjie Zhao, Lillian Sun, Xiaoxia Li
Granulocyte-macrophage colony-stimulating factor (GM-CSF or Csf-2) is a pro-inflammatory mediator implicated in the pathogenesis of various autoimmune diseases. In this issue of Immunity, Spath et al. (2017) show that the dysregulated production of GM-CSF rather than IL-17 induces spontaneous immunopathology in a mouse model of CNS inflammation.
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28225165/the-contrasting-role-of-th17-immunity-in-human-health-and-disease
#3
Edwin Hoe, Jeremy Anderson, Jordan Nathanielsz, Zheng Quan Toh, Rachel Marimla, Anne Balloch, Paul V Licciardi
The human immune system is a tightly regulated network that protects the host from disease. An important aspect of this is the balance between pro-inflammatory Th17 cells and anti-inflammatory Treg cells in maintaining immune homeostasis. Foxp3+ Treg are critical for sustaining immune tolerance through IL-10 and TGF-β while RORγt+ Th17 cells promote immunopathology and auto-inflammatory diseases through the actions of IL-17A, IL-21 and IL-22. Therefore, the imbalance between Treg and Th17 cells can result in serious pathology in many organs and tissues in the body...
February 22, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28224222/immunopathological-characterization-of-human-cutaneous-leishmaniasis-lesions-caused-by-leishmania-viannia-spp-in-amazonian-brazil
#4
Cláudia Maria Castro Gomes, Maria Gloria Teixeira Sousa, Joyce Prieto Bezerra Menezes, Marliane Campos Batista, Ana Carolina Stocco Lima, Walter Belda, Daniel Bradshaw, Monica Elinor Alves Gama, Márcia Dalastra Laurenti, Fernando Tobias Silveira, Carlos Eduardo Pereira Corbett
American cutaneous leishmaniasis (ACL) is a chronic infectious disease caused by different protozoan species of Leishmania, and it is endemic in both tropical and subtropical countries. Using immunohistochemistry, we investigate the density of CD68(+), lysozyme(+), CD1a(+), factor XIIIa(+), CD4(+), CD8(+), CD56(+), interferon (IFN)-γ(+), and inducible NO synthase (iNOS(+)) cells. These cells were analyzed from 22 biopsy samples obtained from the lesions of ACL patients, whose infection was caused by Leishmania (Viannia) spp...
February 21, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28219889/rapid-and-rigorous-il-17a-production-by-a-distinct-subpopulation-of-effector-memory-t-lymphocytes-constitutes-a-novel-mechanism-of-toxic-shock-syndrome-immunopathology
#5
Peter A Szabo, Ankur Goswami, Delfina M Mazzuca, Kyoungok Kim, David B O'Gorman, David A Hess, Ian D Welch, Howard A Young, Bhagirath Singh, John K McCormick, S M Mansour Haeryfar
Toxic shock syndrome (TSS) is caused by staphylococcal and streptococcal superantigens (SAgs) that provoke a swift hyperinflammatory response typified by a cytokine storm. The precipitous decline in the host's clinical status and the lack of targeted therapies for TSS emphasize the need to identify key players of the storm's initial wave. Using a humanized mouse model of TSS and human cells, we herein demonstrate that SAgs elicit in vitro and in vivo IL-17A responses within hours. SAg-triggered human IL-17A production was characterized by remarkably high mRNA stability for this cytokine...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28219579/glomerular-diseases-and-renal-transplantation-pathogenic-pathways-and-evolution-of-therapeutic-interventions
#6
S Marinaki, C Skalioti, J Boletis
Glomerular diseases and renal transplantation are the main fields of nephrology in which the immune system plays a prevalent role. Glomerular diseases have traditionally been attributed to auto-immune conditions, whereas allograft rejection has been considered an allo-immune response. However, common immunopathologic mechanisms that include Toll-like receptors, complement and B-cell activation, as well as genetic and infectious factors appear to be involved in the pathogenesis of both entities. Novel therapeutic regimens directed against specific targets of the immune system show promising results in glomerulopathies as well as in renal transplantation...
March 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28216884/chemical-components-from-aloe-and-their-inhibition-of-indoleamine-2-3-dioxygenase
#7
Ya Nan Sun, Lin Ying Li, Wei Li, Jong Seong Kang, Inkyu Hwang, Young Ho Kim
BACKGROUND: In Korea, Aloe is routinely ingested as a traditional medicine or as a component of health beverages. OBJECTIVE: To research the inhibition of indoleamine 2, 3-dioxygenase (IDO) activities of components from Aloe. MATERIALS AND METHODS: the compounds were isolated by a combination of silica gel and YMC Rp-18 column chromatography, and their structures were identified by analysis of spectroscopic data (1D, 2D-NMR, and MS). All of the isolated compounds were examined for their ability to inhibit IDO, which actively suppresses immune functions by catalyzing the rate limiting reaction in the conversion of tryptophan to kynurenine...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28214859/farnesoid-x-receptor-in-mice-prevents-severe-liver-immunopathology-during-lymphocytic-choriomeningitis-virus-infection
#8
Nadine Honke, Namir Shaabani, Cornelia Hardt, Caroline Krings, Dieter Häussinger, Philipp A Lang, Karl S Lang, Verena Keitel
BACKGROUND: Bile acids (BAs) are steroid molecules that are synthesized in the liver. In addition to their important role as a surfactant in solubilizing lipids and promoting the absorption of lipids in the gastrointestinal tract, they act as inflammagens. The role of BAs and their receptor farnesoid X receptor (FXR) during viral infection has not been studied in detail. METHODS: By using FXR-deficient mice, we investigated the role of bile acid receptor FXR during infection with lymphocytic choriomeningitis virus (LCMV)...
January 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28212734/role-of-granule-proteases-in-the-life-and-death-of-neutrophils
#9
REVIEW
Charaf Benarafa, Hans-Uwe Simon
Neutrophils constitute a crucial component of the innate immune defenses against microbes. Produced in the bone marrow and patrolling in blood vessels, neutrophils are recruited to injured tissues and are immediately active to contain pathogen invasion. Neutrophils undergo programmed cell death by multiple, context-specific pathways, which have consequences on immunopathology and disease outcome. Studies in the last decade indicate additional functions for neutrophils - or a subset of neutrophils - in modulating adaptive responses and tumor progression...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28207788/self-complementary-adeno-associated-virus-serotype-6-mediated-knockdown-of-adamts4-induces-long-term-and-effective-enhancement-of-aggrecan-in-degenerative-human-nucleus-pulposus-cells-a-new-therapeutic-approach-for-intervertebral-disc-disorders
#10
Demissew Shenegelegn Mern, Anja Tschugg, Sebastian Hartmann, Claudius Thomé
Inhibition of intervertebral disc (IVD) degeneration, which is often accompanied by painful inflammatory and immunopathological processes, is challenging. Current IVD gene therapeutic approaches are based on adenoviral gene delivery systems, which are limited by immune reactions to their viral proteins. Their applications in IVDs near to sensitive neural structure could provoke toxicity and immunological side-effects with neurological deficits. Self-complementary adeno-associated virus (scAAV) vectors, which do not express any viral gene and are not linked with any known disease in humans, are attractive therapeutic gene delivery vectors in degenerative IVDs...
2017: PloS One
https://www.readbyqxmd.com/read/28192528/cd8-t-cell-cytotoxicity-mediates-pathology-in-the-skin-by-inflammasome-activation-and-il-1%C3%AE-production
#11
Fernanda O Novais, Augusto M Carvalho, Megan L Clark, Lucas P Carvalho, Daniel P Beiting, Igor E Brodsky, Edgar M Carvalho, Phillip Scott
Deregulated CD8+ T cell cytotoxicity plays a central role in enhancing disease severity in several conditions. However, we have little understanding of the mechanisms by which immunopathology develops as a consequence of cytotoxicity. Using murine models of inflammation induced by the protozoan parasite leishmania, and data obtained from patients with cutaneous leishmaniasis, we uncovered a previously unrecognized role for NLRP3 inflammasome activation and IL-1β release as a detrimental consequence of CD8+ T cell-mediated cytotoxicity, ultimately resulting in chronic inflammation...
February 13, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28184993/pathogenic-implications-of-cerebrospinal-fluid-barrier-pathology-in-neuromyelitis-optica
#12
Yong Guo, Stephen D Weigand, Bogdan F Popescu, Vanda A Lennon, Joseph E Parisi, Sean J Pittock, Natalie E Parks, Stacey L Clardy, Charles L Howe, Claudia F Lucchinetti
Pathogenic autoantibodies associated with neuromyelitis optica (NMO) induce disease by targeting aquaporin-4 (AQP4) water channels enriched on astrocytic endfeet at blood-brain interfaces. AQP4 is also expressed at cerebrospinal fluid (CSF)-brain interfaces, such as the pial glia limitans and the ependyma and at the choroid plexus blood-CSF barrier. However, little is known regarding pathology at these sites in NMO. Therefore, we evaluated AQP4 expression, microglial reactivity, and complement deposition at pial and ependymal surfaces and in the fourth ventricle choroid plexus in 23 autopsy cases with clinically and/or pathologically confirmed NMO or NMO spectrum disorder...
February 9, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28178437/gerald-loewi-a-major-contributor-to-the-new-era-of-rheumatology-thinking
#13
Michael Denman
Dr Gerald Loewi was Senior Research Scientist and Consultant Pathologist at the Medical Research Council (MRC) Rheumatism Research Unit at Taplow, England and subsequently the MRC Clinical Research Centre, Harrow, England. An immunologist with a background in pathology, he made major contributions to our understanding of the immunopathology of rheumatoid arthritis and other rheumatic disorders. With his colleagues, he developed a more sophisticated concept of what were initially thought to be primary autoimmune or degenerative diseases but are now recognized as much more complex disease processes...
January 30, 2017: Rambam Maimonides Medical Journal
https://www.readbyqxmd.com/read/28173836/complex-regulation-of-neutrophil-derived-mmp-9-secretion-in-central-nervous-system-tuberculosis
#14
Catherine W M Ong, Przemyslaw J Pabisiak, Sara Brilha, Poonam Singh, Federico Roncaroli, Paul T Elkington, Jon S Friedland
BACKGROUND: Central nervous system tuberculosis (CNS-TB) may be fatal even with treatment. Neutrophils are the key mediators of TB immunopathology, and raised CSF matrix metalloproteinase-9 (MMP-9) which correlates to neutrophil count in CNS-TB is associated with neurological deficit and death. The mechanisms by which neutrophils drive TB-associated CNS matrix destruction are not clearly defined. METHODS: Human brain biopsies with histologically proven CNS-TB were stained for neutrophils, neutrophil elastase, and MMP-9...
February 7, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28169000/regulation-and-functions-of-nlrp3-inflammasome-during-influenza-virus-infection
#15
Teneema Kuriakose, Thirumala-Devi Kanneganti
The NLRP3 inflammasome constitutes a major antiviral host defense mechanism during influenza virus infection. Inflammasome assembly in virus-infected cells facilitates autocatalytic processing of pro-caspase-1 and subsequent cleavage and secretion of proinflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome is critical for induction of both innate and adaptive immune responses during influenza virus infection. Inflammasome-dependent antiviral responses also regulate immunopathology and tissue repair in the infected lungs...
February 3, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28167629/il-10-plays-opposing-roles-during-staphylococcus-aureus-systemic-and-localized-infections
#16
John M Leech, Keenan A Lacey, Michelle E Mulcahy, Eva Medina, Rachel M McLoughlin
IL-10 is a potent anti-inflammatory mediator that plays a crucial role in limiting host immunopathology during bacterial infections by controlling effector T cell activation. Staphylococcus aureus has previously been shown to manipulate the IL-10 response as a mechanism of immune evasion during chronic systemic and biofilm models of infection. In the present study, we demonstrate divergent roles for IL-10 depending on the site of infection. During acute systemic S. aureus infection, IL-10 plays an important protective role and is required to prevent bacterial dissemination and host morbidity by controlling effector T cells and the associated downstream hyperactivation of inflammatory phagocytes, which are capable of host tissue damage...
February 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28157451/the-role-of-nod-like-receptors-in-pulmonary-infection
#17
Kristin M Wiese, Bria M Coates, Karen M Ridge
Pneumonia is caused by both viral and bacterial pathogens and is responsible for a significant health burden in the Unites States. The innate immune system is the human body's first line of defense against these pathogens. The recognition of invading pathogens via pattern recognition receptors (PRRs) leads to proinflammatory cytokine and chemokine production followed by recruitment and activation of effector immune cells. The nonspecific inflammatory nature of the innate immune response can result in immunopathology that is detrimental to the host...
February 3, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28153825/tissue-tolerance-a-distinct-concept-to-control-acute-gvhd-severity
#18
Shin-Rong Wu, Pavan Reddy
Target tissue damage occurs as a consequence of pathological immune responses following allogeneic stem cell transplantation resulting in acute graft-versus-host disease (GVHD). Among those who study infections in plants, it is well recognized that tissues play a distinct role from the immune system in mediating disease severity. Recently, this has also been appreciated in mammals. However, the severity of immunopathology in the context of alloimmune diseases such as acute GVHD has been mainly understood and managed by direct targeting of immune cells to generate immune tolerance...
February 2, 2017: Blood
https://www.readbyqxmd.com/read/28141856/transcriptional-profiling-in-experimental-visceral-leishmaniasis-reveals-a-broad-splenic-inflammatory-environment-that-conditions-macrophages-toward-a-disease-promoting-phenotype
#19
Fanping Kong, Omar A Saldarriaga, Heidi Spratt, E Yaneth Osorio, Bruno L Travi, Bruce A Luxon, Peter C Melby
Visceral Leishmaniasis (VL), caused by the intracellular protozoan Leishmania donovani, is characterized by relentlessly increasing visceral parasite replication, cachexia, massive splenomegaly, pancytopenia and ultimately death. Progressive disease is considered to be due to impaired effector T cell function and/or failure of macrophages to be activated to kill the intracellular parasite. In previous studies, we used the Syrian hamster (Mesocricetus auratus) as a model because it mimics the progressive nature of active human VL...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28138136/t-cell-responses-in-the-central-nervous-system
#20
REVIEW
Thomas Korn, Axel Kallies
T cells are required for immune surveillance of the central nervous system (CNS); however, they can also induce severe immunopathology in the context of both viral infections and autoimmunity. The mechanisms that are involved in the priming and recruitment of T cells to the CNS are only partially understood, but there has been renewed interest in this topic since the 'rediscovery' of lymphatic drainage from the CNS. Moreover, tissue-resident memory T cells have been detected in the CNS and are increasingly recognized as an autonomous line of host defence...
January 31, 2017: Nature Reviews. Immunology
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