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https://www.readbyqxmd.com/read/29332936/tissue-specific-immunopathology-during-malaria-infection
#1
REVIEW
Cevayir Coban, Michelle Sue Jann Lee, Ken J Ishii
Systemic inflammation mediated by Plasmodium parasites is central to malaria disease and its complications. Plasmodium parasites reside in erythrocytes and can theoretically reach all host tissues via the circulation. However, actual interactions between parasitized erythrocytes and host tissues, along with the consequent damage and pathological changes, are limited locally to specific tissue sites. Such tissue specificity of the parasite can alter the outcome of malaria disease, determining whether acute or chronic complications occur...
January 15, 2018: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/29330423/t-cell-immunity-to-zika-virus-targets-immunodominant-epitopes-that-show-cross-reactivity-with-other-flaviviruses
#2
C J Reynolds, O M Suleyman, A M Ortega-Prieto, J K Skelton, P Bonnesoeur, A Blohm, V Carregaro, J S Silva, E A James, B Maillère, M Dorner, R J Boyton, D M Altmann
Zika virus (ZIKV) Infection has several outcomes from asymptomatic exposure to rash, conjunctivitis, Guillain-Barré syndrome or congenital Zika syndrome. Analysis of ZIKV immunity is confounded by the fact that several related Flaviviruses infect humans, including Dengue virus 1-4, West Nile virus and Yellow Fever virus. HLA class II restricted T cell cross-reactivity between ZIKV and other Flaviviruses infection(s) or vaccination may contribute to protection or to enhanced immunopathology. We mapped immunodominant, HLA class II restricted, CD4 epitopes from ZIKV Envelope (Env), and Non-structural (NS) NS1, NS3 and NS5 antigens in HLA class II transgenic mice...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329934/application-of-our-understanding-of-pathogenesis-of-herpetic-stromal-keratitis-for-novel-therapy
#3
Naveen K Rajasagi, Barry T Rouse
HSV-1 ocular infection can cause herpes stromal keratitis (SK), an immunopathological lesion. Frequent recurrences can lead to progressive corneal scaring which can result in vision impairment if left untreated. Currently, the acute and epithelial forms of SK are usually controlled using anti-viral drugs. However, chronic forms of SK which are inflammatory in nature, require the addition of a topical corticosteroid to the anti-viral treatment regimen. In this review, we highlight the essential events involved in SK pathogenesis which can be targeted for improved therapy...
January 9, 2018: Microbes and Infection
https://www.readbyqxmd.com/read/29315518/hyaluronan-binding-by-cd44-reduces-the-memory-potential-of-activated-murine-cd8-t-cells
#4
Sally S M Lee-Sayer, Nina Maeshima, Meghan N Dougan, Anita Dahiya, Arif A Arif, Manisha Dosanjh, Christopher A Maxwell, Pauline Johnson
Expansion and death of effector CD8 T cells are regulated to limit immunopathology and cells that escape contraction go on to generate immunological memory. CD44, a receptor for the extracellular matrix component hyaluronan, is a marker of activated and memory T cells. Here, we show with a murine model that the increase in CD44 expression and hyaluronan binding induced upon CD8 T cell activation was proportional to the strength of TCR engagement, thereby identifying the most strongly activated T cells. When CD44-/- and CD44+/+ OT-I CD8 T cells were adoptively transferred into mice challenged with Listeria-OVA, there was a slight increase in the percentage of CD44+/+ cells at the effector site...
January 8, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29312814/on-revealing-the-gene-targets-of-ebola-virus-micrornas-involved-in-the-human-skin-microbiome
#5
Pei-Chun Hsu, Bin-Hao Chiou, Chun-Ming Huang
Ebola virus, a negative-sense single-stranded RNA virus, causes severe viral hemorrhagic fever and has a high mortality rate. Histopathological and immunopathological analyses of Ebola virus have revealed that histopathological changes in skin tissue are associated with various degrees of endothelial cell swelling and necrosis. The interactions of microbes within or on a host are a crucial for the skin immune shield. The discovery of microRNAs (miRNAs) in Ebola virus implies that immune escape, endothelial cell rupture, and tissue dissolution during Ebola virus infection are a result of the effects of Ebola virus miRNAs...
2018: PeerJ
https://www.readbyqxmd.com/read/29311359/the-effects-of-dendritic-cell-hypersensitivity-on-persistent-viral-infection
#6
Jennifer S Tsau, Xin Huang, Chen-Yen Lai, Stephen M Hedrick
Caspase-8 (CASP8) is known as an executioner of apoptosis, but more recent studies have shown that it participates in the regulation of necroptosis and innate immunity. In this study, we show that CASP8 negatively regulates retinoic acid-inducible gene I (RIG-I) signaling such that, in its absence, stimulation of the RIG-I pathway in dendritic cells (DCs) produced modestly enhanced activation of IFN regulatory factor 3 with correspondingly greater amounts of proinflammatory cytokines. In addition, mice lacking DC-specific CASP8 (dcCasp8-/- mice) develop age-dependent symptoms of autoimmune disease characterized by hyperactive DCs and T cells, spleen and liver immunopathology, and the appearance of Th1-polarized CD4+ T cells...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29306173/blocking-osteopontin-fibronectin-interactions-reduce-extracellular-fibronectin-deployment-and-arthritic-immunopathology
#7
Brij Bhushan Mehta, Saniya Sharma, Rakesh K Vasishta, Ramesh K Sen, Aman Sharma, Manni Luthra-Guptasarma
Elevated levels of a thrombin-cleaved fragment of osteopontin (OPNT) are seen in synovial fluid (SF) and tissues of rheumatoid arthritis (RA) patients. OPNT binds to integrins on cell surfaces, inducing adhesion, migration and survival of inflammatory cells in the synovial joints, where OPNT binds to fibronectin to link fibroblast-like synoviocytes (FLS) with B cells, stimulating the latter to produce inflammatory cytokines. Our aim was to block OPNT-fibronectin interactions and examine whether this reduces inflammation...
January 3, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29300777/internal-genes-of-a-highly-pathogenic-h5n1-influenza-virus-determine-high-viral-replication-in-myeloid-cells-and-severe-outcome-of-infection-in-mice
#8
Hui Li, Konrad C Bradley, Jason S Long, Rebecca Frise, Jonathan W Ashcroft, Lorian C Hartgroves, Holly Shelton, Spyridon Makris, Cecilia Johansson, Bin Cao, Wendy S Barclay
The highly pathogenic avian influenza (HPAI) H5N1 influenza virus has been a public health concern for more than a decade because of its frequent zoonoses and the high case fatality rate associated with human infections. Severe disease following H5N1 influenza infection is often associated with dysregulated host innate immune response also known as cytokine storm but the virological and cellular basis of these responses has not been clearly described. We rescued a series of 6:2 reassortant viruses that combined a PR8 HA/NA pairing with the internal gene segments from human adapted H1N1, H3N2, or avian H5N1 viruses and found that mice infected with the virus with H5N1 internal genes suffered severe weight loss associated with increased lung cytokines but not high viral load...
January 4, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29298833/production-of-il-17-by-mait-cells-is-increased-in-multiple-sclerosis-and-is-associated-with-il-7-receptor-expression
#9
Anne Willing, Jan Jäger, Stefanie Reinhardt, Nina Kursawe, Manuel A Friese
Multiple sclerosis (MS) is a T cell-driven inflammatory disease of the CNS. Research on T cell subsets involved in MS pathogenesis has mainly focused on classical CD4+ T cells, especially Th17 cells, as they produce the proinflammatory, MS-associated cytokine IL-17. However, the abundant unconventional mucosal-associated invariant T (MAIT) cells are also able to produce IL-17. MAIT cells are characterized by high CD161 expression and a semi-invariant Vα7.2 TCR, with which they recognize bacterial and yeast Ags derived from the riboflavin (vitamin B2) metabolism...
January 3, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29297752/il4-interleukin-4-induces-autophagy-in-b-cells-leading-to-exacerbated-asthma
#10
Fucan Xia, Changwen Deng, Yanyan Jiang, Yulan Qu, Jiewen Deng, Zhijian Cai, Yuanyuan Ding, Zhenhong Guo, Jianli Wang
Allergic asthma is a common airway inflammatory disease in which B cells play important roles through IgE production and antigen presentation. SNP (single nucleotide polymorphism) analysis showed that Atg (autophagy-related) allele mutations are involved in asthma. It has been demonstrated that macroautophagy/autophagy is essential for B cell survival, plasma cell differentiation and immunological memory maintenance. However, whether B cell autophagy participates in asthma pathogenesis remains to be investigated...
January 3, 2018: Autophagy
https://www.readbyqxmd.com/read/29297501/t-bet-independent-th1-response-induces-intestinal-immunopathology-during-toxoplasma-gondii-infection
#11
Américo H López-Yglesias, Elise Burger, Alessandra Araujo, Andrew T Martin, Felix Yarovinsky
Coordinated production of IFN-γ by innate and adaptive immune cells is central for host defense, but can also trigger immunopathology. The investigation of the lymphoid cell-specific contribution to the IFN-γ-mediated intestinal pathology during Toxoplasma gondii infection identified CD4+ T cells as a key cell population responsible for IFN-γ-dependent intestinal inflammation and Paneth cell loss, where T-bet-dependent group 1 innate lymphoid cells have a minor role in driving the parasite-induced immunopathology...
January 3, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29296203/the-pathogenesis-of-diclofenac-induced-immunoallergic-hepatitis-in-a-canine-model-of-liver-injury
#12
Saravanakumar Selvaraj, Jung-Hwa Oh, Reinhard Spanel, Florian Länger, Hyoung-Yun Han, Eun-Hee Lee, Seokjoo Yoon, Jürgen Borlak
Hypersensitivity to non-steroidal anti-inflammatory drugs is a common adverse drug reaction and may result in serious inflammatory reactions of the liver. To investigate mechanism of immunoallergic hepatitis beagle dogs were given 1 or 3 mg/kg/day (HD) oral diclofenac for 28 days. HD diclofenac treatment caused liver function test abnormalities, reduced haematocrit and haemoglobin but induced reticulocyte, WBC, platelet, neutrophil and eosinophil counts. Histopathology evidenced hepatic steatosis and glycogen depletion, apoptosis, acute lobular hepatitis, granulomas and mastocytosis...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295868/the-immunoproteasome-specific-inhibitor-onx-0914-reverses-susceptibility-to-acute-viral-myocarditis
#13
Nadine Althof, Carl Christoph Goetzke, Meike Kespohl, Karolin Voss, Arnd Heuser, Sandra Pinkert, Ziya Kaya, Karin Klingel, Antje Beling
Severe heart pathology upon virus infection is closely associated with the immunological equipment of the host. Since there is no specific treatment available, current research focuses on identifying new drug targets to positively modulate predisposing immune factors. Utilizing a murine model with high susceptibility to coxsackievirus B3-induced myocarditis, this study describes ONX 0914-an immunoproteasome-specific inhibitor-as highly protective during severe heart disease. Represented by reduced heart infiltration of monocytes/macrophages and diminished organ damage, ONX 0914 treatment reversed fulminant pathology...
January 2, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29286160/identification-and-characterization-of-epitopes-from-influenza-a-virus-hemagglutinin-that-induce-broadly-cross-reactive-antibodies
#14
Yuan Li, Hanyu Hu, Zongli Qi, Jingying Sun, Yan Li, Qing Feng, Chunyan Guo, Haifang Wang, Penghua Zhao, Yang Liu, Xiangrong Zhao, Guanghua Wang, Hai Zhang, Libin Liu, Jun Hu
Influenza is the most common infectious disease and is caused by influenza A virus (IAV) infection. Hemagglutinin (HA) is an important viral protein of influenza A and is a major component of current IAV vaccines. The side effects associated with IAV vaccination are well studied; however, the HA‑induced immunopathological changes have remained largely elusive. The primary objective of the present study was to determine the tissue cross‑reactive epitopes of HA proteins. Monoclonal antibodies (McAbs) were generated according to traditional methods using purified HA proteins from influenza vaccine lysates...
December 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29284469/both-inflammatory-and-regulatory-cytokine-responses-to-malaria-are-blunted-with-increasing-age-in-highly-exposed-children
#15
Lila Farrington, Hilary Vance, John Rek, Mary Prahl, Prasanna Jagannathan, Agaba Katureebe, Emmanuel Arinaitwe, Moses R Kamya, Grant Dorsey, Margaret E Feeney
BACKGROUND: Young children are at greatest risk for malaria-associated morbidity and mortality. The immune response of young children differs in fundamental ways from that of adults, and these differences likely contribute to the increased susceptibility of children to severe malaria and to their delayed development of immunity. Elevated levels of pro-inflammatory cytokines and chemokines in the peripheral blood during acute infection contribute to the control of parasitaemia, but are also responsible for much of the immunopathology seen during symptomatic disease...
December 29, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29282304/type-2-cysteinyl-leukotriene-receptors-drive-il-33-dependent-type-2-immunopathology-and-aspirin-sensitivity
#16
Tao Liu, Nora A Barrett, Yoshihide Kanaoka, Eri Yoshimoto, Denise Garofalo, Haley Cirka, Chunli Feng, Joshua A Boyce
Cysteinyl leukotrienes (cysLTs) facilitate mucosal type 2 immunopathology by incompletely understood mechanisms. Aspirin-exacerbated respiratory disease, a severe asthma subtype, is characterized by exaggerated eosinophilic respiratory inflammation and reactions to aspirin, each involving the marked overproduction of cysLTs. Here we demonstrate that the type 2 cysLT receptor (CysLT2R), which is not targeted by available drugs, is required in two different models to amplify eosinophilic airway inflammation via induced expression of IL-33 by lung epithelial cells...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29275469/tryptophan-catabolism-and-cancer-immunotherapy-targeting-ido-mediated-immune-suppression
#17
Adaobi Amobi, Feng Qian, Amit A Lugade, Kunle Odunsi
Over the last decade, tryptophan catabolism has been firmly established as a powerful mechanism of innate and adaptive immune tolerance. The catabolism of tryptophan is a central pathway maintaining homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses. This is driven by the key and rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1) and tryptophan-2,3-dioxygenase 2 (TDO), resulting in local depletion of tryptophan, while tryptophan catabolites accumulate, including kynurenine and its derivatives, depending on the presence of downstream enzymes in the kynurenine pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29273643/plasmacytoid-dendritic-cells-protect-from-viral-bronchiolitis-and-asthma-through-semaphorin-4a-mediated-t-reg-expansion
#18
Jason P Lynch, Rhiannon B Werder, Zhixuan Loh, Md Al Amin Sikder, Bodie Curren, Vivian Zhang, Matthew J Rogers, Katie Lane, Jennifer Simpson, Stuart B Mazzone, Kirsten Spann, John Hayball, Kerrilyn Diener, Mark L Everard, Christopher C Blyth, Christian Forstner, Paul G Dennis, Nida Murtaza, Mark Morrison, Páraic Ó Cuív, Ping Zhang, Ashraful Haque, Geoffrey R Hill, Peter D Sly, John W Upham, Simon Phipps
Respiratory syncytial virus-bronchiolitis is a major independent risk factor for subsequent asthma, but the causal mechanisms remain obscure. We identified that transient plasmacytoid dendritic cell (pDC) depletion during primary Pneumovirus infection alone predisposed to severe bronchiolitis in early life and subsequent asthma in later life after reinfection. pDC depletion ablated interferon production and increased viral load; however, the heightened immunopathology and susceptibility to subsequent asthma stemmed from a failure to expand functional neuropilin-1+ regulatory T (T reg) cells in the absence of pDC-derived semaphorin 4a (Sema4a)...
December 22, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29258535/lytic-viral-replication-and-immunopathology-in-a-cytomegalovirus-induced-mouse-model-of-secondary-hemophagocytic-lymphohistiocytosis
#19
Ellen Brisse, Maya Imbrechts, Tania Mitera, Jessica Vandenhaute, Carine H Wouters, Robert Snoeck, Graciela Andrei, Patrick Matthys
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological disorder caused by unbridled activation of T cells and macrophages, culminating in a life-threatening cytokine storm. A genetic and acquired subtype are distinguished, termed primary and secondary HLH, respectively. Clinical manifestations of both forms are frequently preceded by a viral infection, predominantly with herpesviruses. The exact role of the viral infection in the development of the hemophagocytic syndrome remains to be further elucidated...
December 19, 2017: Virology Journal
https://www.readbyqxmd.com/read/29246870/metabolic-defects-in-multiple-sclerosis
#20
REVIEW
Reginald C Adiele, Chiedukam A Adiele
Brain injuries in multiple sclerosis (MS) involve immunopathological, structural and metabolic defects on myelin sheath, oligodendrocytes (OLs), axons and neurons suggesting that different cellular mechanisms ultimately result in the formation of MS plaques, demyelination, inflammation and brain damage. Bioenergetics, oxygen and ion metabolism dominate the metabolic and biochemical pathways that maintain neuronal viability and impulse transmission which directly or indirectly point to mitochondrial integrity and adenosine triphosphate (ATP) availability indicating the involvement of mitochondria in the pathogenesis of MS...
December 13, 2017: Mitochondrion
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