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https://www.readbyqxmd.com/read/28221171/pathogenesis-of-severe-pneumonia-advances-and-knowledge-gaps
#1
Joseph P Mizgerd
PURPOSE OF REVIEW: Pneumonia is a common disease that becomes severe in a subset of patients, dependent on host biology including mechanisms of immune resistance and tissue resilience. This review emphasizes discoveries in pneumonia biology from 2016, highlighting questions and directions that are especially pressing or newly emerging. RECENT FINDINGS: Novel cell-cell interactions mediating innate immune responses against microbes in the lung have been elucidated, between distinct leukocyte subtypes as well as between leukocytes and the structural cells of the lung...
February 17, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28219080/survival-of-tissue-resident-memory-t-cells-requires-exogenous-lipid-uptake-and-metabolism
#2
Youdong Pan, Tian Tian, Chang Ook Park, Serena Y Lofftus, Shenglin Mei, Xing Liu, Chi Luo, John T O'Malley, Ahmed Gehad, Jessica E Teague, Sherrie J Divito, Robert Fuhlbrigge, Pere Puigserver, James G Krueger, Gökhan S Hotamisligil, Rachael A Clark, Thomas S Kupper
Tissue-resident memory T (TRM) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. However, the biological pathways that enable the long-term survival of TRM cells are obscure. Here we show that mouse CD8(+) TRM cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). We further show that T-cell-specific deficiency of Fabp4 and Fabp5 (Fabp4/Fabp5) impairs exogenous free fatty acid (FFA) uptake by CD8(+) TRM cells and greatly reduces their long-term survival in vivo, while having no effect on the survival of central memory T (TCM) cells in lymph nodes...
February 20, 2017: Nature
https://www.readbyqxmd.com/read/28214619/transition-from-non-fickian-to-fickian-longitudinal-transport-through-3-d-rough-fractures-scale-in-sensitivity-and-roughness-dependence
#3
Lichun Wang, M Bayani Cardenas
Understanding transport in rough fractures from non-Fickian to Fickian regimes and the prediction of non-Fickian transport is critical for the development of new transport theories and many practical applications. Through computational experiments that fall within the macrodispersion regime, we first simulated and analyzed solute transport through synthetic rough fractures with stationary geometrical properties (i.e., fracture roughness σb/〈b〉 and correlation length λ, where b refers to aperture with its standard deviation σb and arithmetic mean 〈b〉) across increasing fracture longitudinal transport domain length L, with L/λ ranging from 2...
February 4, 2017: Journal of Contaminant Hydrology
https://www.readbyqxmd.com/read/28214226/cd49a-expression-defines-tissue-resident-cd8-t-cells-poised-for-cytotoxic-function-in-human-skin
#4
Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28212742/demonstration-of-tissue-resident-memory-cd8-t-cells-in-insulitic-lesions-in-adult-patients-with-recent-onset-type-1-diabetes
#5
Enida Kuric, Peter Seiron, Lars Krogvold, Bjørn Edwin, Trond Buanes, Kristian F Hanssen, Oskar Skog, Knut Dahl-Jørgensen, Olle Korsgren
Subtypes of CD8(+) T cells in insulitic lesions in biopsy specimens from six subjects with recent-onset type 1 diabetes (T1D) and six nondiabetic matched controls were analyzed using simultaneous multicolor immunofluorescence. Also, insulitic islets based on accumulation of CD3(+) T cells were microdissected with laser-capture microscopy, and gene transcripts associated with inflammation and autoimmunity were analyzed. We found a substantial proportion, 43%, of the CD8(+) T cells in the insulitic lesions to display a tissue resident memory T cell (TRM) (CD8(+)CD69(+)CD103(+)) phenotype in T1D subjects...
March 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28195063/generation-of-membrane-bound-catechol-o-methyl-transferase-deficient-mice-with-disctinct-sex-dependent-behavioral-phenotype
#6
A Tammimaki, A Aonurm-Helm, F P Zhang, M Poutanen, G Duran-Torres, A Garcia-Horsman, P T Mannisto
Catechol-O-methyltransferase (COMT) has two isoforms: soluble (S-COMT), which resides in the cytoplasm, and membrane-bound (MB-MT), anchored to intracellular membranes. COMT is involved in the O-methylation of L-DOPA, dopamine and other catechols. The exact role of MB-COMT is still mostly unclear. We wanted to create a novel genetically modified mouse model that specifically lacks MB-COMT activity and to study their behavioral phenotype. MB-COMT knock-in mutant mice were generated by introducing two point mutations in exon 2 of the Comt gene (ATGCTG->GAGCTC disabling the function of the P2 promoter and allowing only the P1-regulated S-COMT transcription...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28187750/study-on-age-dependent-pre-existing-2009-pandemic-influenza-virus-t-and-b-cell-responses-from-chinese-population
#7
Jin Lv, Zhen-Yong Ren, Ying-Ying Zhang, Yun-E Liu, Jun Gao, Kun Yao, Dan Feng, Zhen-Yuan Li, Xin Feng, Yun-Xi Liu, Na Jia
BACKGROUND: The outbreak of the 2009 H1N1 influenza pandemic (H1N1pdm) affected thousands of people in Mexico and the United States, and spread rapidly throughout the world from April 2009 to July 2010. To explore the age-specific prevalence of seroprotection against H1N1pdm infection, we estimated pre-existing humoral and cellular immunities of residents in Northern China against H1N1pdm and seasonal H1N1 virus in an age-dependent manner. METHODS: Anonymous serum samples were collected from 1425 to 1434 adult healthy individuals before and after the pandemic outbreak, and then grouped by birth year 1913-1990...
February 10, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28182750/chemoprophylaxis-with-sporozoite-immunization-in-p-knowlesi-rhesus-monkeys-confers-protection-and-elicits-sporozoite-specific-memory-t-cells-in-the-liver
#8
Sathit Pichyangkul, Michele D Spring, Kosol Yongvanitchit, Utaiwan Kum-Arb, Amporn Limsalakpetch, Rawiwan Im-Erbsin, Ratawan Ubalee, Pattaraporn Vanachayangkul, Edmond J Remarque, Evelina Angov, Philip L Smith, David L Saunders
Whole malaria sporozoite vaccine regimens are promising new strategies, and some candidates have demonstrated high rates of durable clinical protection associated with memory T cell responses. Little is known about the anatomical distribution of memory T cells following whole sporozoite vaccines, and immunization of nonhuman primates can be used as a relevant model for humans. We conducted a chemoprophylaxis with sporozoite (CPS) immunization in P. knowlesi rhesus monkeys and challenged via mosquito bites. Half of CPS immunized animals developed complete protection, with a marked delay in parasitemia demonstrated in the other half...
2017: PloS One
https://www.readbyqxmd.com/read/28179523/progesterone-based-contraceptives-reduce-adaptive-immune-responses-and-protection-against-sequential-influenza-a-virus-infections
#9
Olivia J Hall, Raffael Nachbagauer, Meghan S Vermillion, Ashley L Fink, Vanessa Phuong, Florian Krammer, Sabra L Klein
In addition to their intended use, progesterone (P4)-based contraceptives promote anti-inflammatory immune responses, yet their effects on the outcome of infectious diseases, including influenza A virus (IAV), are rarely evaluated. To evaluate their impact on immune responses to sequential IAV infections, adult female mice were treated with placebo or one of two progestins, P4 or levonorgestrel (LNG), and infected with mouse adapted (ma) H1N1 virus. Treatment with P4 or LNG reduced morbidity, but had no effect on pulmonary virus titers, during primary H1N1 infection as compared to placebo treatment...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28164171/diminished-cd103-%C3%AE-e%C3%AE-7-expression-on-resident-t-cells-from-the-female-genital-tract-of-hiv-positive-women
#10
David C Moylan, Paul A Goepfert, Mirjam-Colette Kempf, Michael S Saag, Holly E Richter, Jiri Mestecky, Steffanie Sabbaj
BACKGROUND: Tissue resident memory T cells (TrM) provide an enhanced response against infection at mucosal surfaces, yet their function has not been extensively studied in humans, including the female genital tract (FGT). METHODS: Using polychromatic flow cytometry, we studied TrM cells, defined as CD62L-CCR7-CD103(+)CD69(+) CD4(+) and CD8(+) T cells in mucosa-derived T cells from healthy and HIV-positive women. RESULTS: We demonstrate that TrM are present in the FGT of healthy and HIV-positive women...
October 2016: Pathogens & Immunity
https://www.readbyqxmd.com/read/28159905/cutting-edge-tissue-resident-memory-t-cells-generated-by-multiple-immunizations-or-localized-deposition-provide-enhanced-immunity
#11
Brooke Davies, Julia E Prier, Claerwen M Jones, Thomas Gebhardt, Francis R Carbone, Laura K Mackay
Tissue-resident memory T cells (TRM) have been shown to afford superior protection against infection, particularly against pathogens that enter via the epithelial surfaces of the body. Although TRM are often concentrated at sites of prior infection, it has been shown that TRM can disseminate throughout the body. We examined the relative effectiveness of global versus targeted CD8(+) TRM lodgment in skin. The site of initial T cell priming made little difference to skin lodgement, whereas local inflammation and Ag recognition enhanced TRM accumulation and retention...
February 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28159532/a-cross-sectional-survey-of-the-access-of-older-people-in-the-scottish-highlands-to-general-medical-practices-community-pharmacies-and-prescription-medicines
#12
Gordon F Rushworth, Scott Cunningham, Sharon Pfleger, Jenny Hall, Derek Stewart
BACKGROUND: Access to medicines and healthcare is more problematic in remote and rural areas. OBJECTIVES: To quantify issues of access to general practitioners (GPs), community pharmacies and prescribed medicines in older people resident in the Scottish Highlands. METHODS: Anonymized questionnaires were mailed to a random sample of 2000 older people (≥60 years) resident in the Scottish Highlands. Questionnaire items were: access and convenience to GP and pharmacy services (10 items); prescribed medicines (13 items); attitudinal statements based on the Theoretical Domains Framework (12 items); quality of life (SF8, 8 items); and demographics (12 items)...
January 25, 2017: Research in Social & Administrative Pharmacy: RSAP
https://www.readbyqxmd.com/read/28142201/lymph-node-and-circulating-t-cell-characteristics-are-strongly-correlated-in-end-stage-renal-disease-patients-but-highly-differentiated-t-cells-reside-within-the-circulation
#13
Burç Dedeoglu, Annelies E de Weerd, Ling Huang, Anton W Langerak, Frank J Dor, Mariska Klepper, Wenda Verschoor, Derek Reijerkerk, Carla C Baan, Nicolle H R Litjens, Michiel G H Betjes
BACKGROUND: Ageing is associated with changes in the peripheral T-cell immune system, which can be significantly influenced by latent cytomegalovirus (CMV) infection. To what extent changes in circulating T-cell populations correlate with T-cell composition of the lymph node (LN) is unclear, but crucial for a comprehensive understanding of the T-cell system. METHODS: T cells from peripheral blood (PB) and LN of end-stage renal disease patients were analyzed for frequency of recent thymic emigrants using CD31 expression and T-cell receptor excision circle content, relative telomere length and expression of differentiation markers...
January 31, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28140404/particulate-air-pollutants-apoe-alleles-and-their-contributions-to-cognitive-impairment-in-older-women-and-to-amyloidogenesis-in-experimental-models
#14
M Cacciottolo, X Wang, I Driscoll, N Woodward, A Saffari, J Reyes, M L Serre, W Vizuete, C Sioutas, T E Morgan, M Gatz, H C Chui, S A Shumaker, S M Resnick, M A Espeland, C E Finch, J C Chen
Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer's disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women's Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers...
January 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28138136/t-cell-responses-in-the-central-nervous-system
#15
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
https://www.readbyqxmd.com/read/28129888/alzheimer-s-disease-innate-immunity-gone-awry
#16
Theodore B VanItallie
Inflammation is an immune activity designed to protect the host from pathogens and noxious agents. In its low-intensity form, presence of an inflammatory process must be inferred from appropriate biomarkers. Occult neuroinflammation is not just secondary to Alzheimer's disease (AD) but may contribute to its pathogenesis and promote its progression. A leaky blood-brain barrier (BBB) has been observed in early AD and may play a role in its initiation and development. Studies of the temporal evolution of AD's biomarkers have shown that, in AD, the brain's amyloid burden correlates poorly with cognitive decline...
January 11, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28122626/developing-a-dementia-specific-health-state-classification-system-for-a-new-preference-based-instrument-ad-5d
#17
Kim-Huong Nguyen, Brendan Mulhern, Sanjeewa Kularatna, Joshua Byrnes, Wendy Moyle, Tracy Comans
BACKGROUND: With an ageing population, the number of people with dementia is rising. The economic impact on the health care system is considerable and new treatment methods and approaches to dementia care must be cost effective. Economic evaluation requires valid patient reported outcome measures, and this study aims to develop a dementia-specific health state classification system based on the Quality of Life for Alzheimer's disease (QOL-AD) instrument (nursing home version). This classification system will subsequently be valued to generate a preference-based measure for use in the economic evaluation of interventions for people with dementia...
January 25, 2017: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/28112260/an-altered-endometrial-cd8-tissue-resident-memory-t-cell-population-in-recurrent-miscarriage
#18
J H Southcombe, G Mounce, K McGee, A Elghajiji, J Brosens, S Quenby, T Child, I Granne
When trying to conceive 1% of couples have recurrent miscarriages, defined as three or more consecutive pregnancy losses. This is not accounted for by the known incidence of chromosomal aneuploidy in miscarriage, and it has been suggested that there is an immunological aetiology. The endometrial mucosa is populated by a variety of immune cells which in addition to providing host pathogen immunity must facilitate pregnancy. Here we characterise the endometrial CD8-T cell population during the embryonic window of implantation and find that the majority of cells are tissue resident memory T cells with high levels of CD69 and CD103 expression, proteins that prevent cells egress...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28108204/the-dietary-approaches-to-stop-hypertension-diet-cognitive-function-and-cognitive-decline-in-american-older-women
#19
Agnes A M Berendsen, Jae H Kang, Ondine van de Rest, Edith J M Feskens, Lisette C P G M de Groot, Francine Grodstein
OBJECTIVES: To examine the association between long-term adherence to the Dietary Approaches to Stop Hypertension (DASH) diet with cognitive function and decline in older American women. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study, a cohort of registered nurses residing in 11 US states. PARTICIPANTS: A total of 16,144 women from the Nurses' Health Study, aged ≥70 years, who underwent cognitive testing a total of 4 times by telephone from 1995 to 2001 (baseline), with multiple dietary assessments between 1984 and the first cognitive examination...
January 17, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28102212/erratum-programs-for-the-persistence-vigilance-and-control-of-human-cd8-lung-resident-memory-t-cells
#20
Pleun Hombrink, Christina Helbig, Ronald A Backer, Berber Piet, Anna E Oja, Regina Stark, Giso Brasser, Aldo Jongejan, René E Jonkers, Benjamin Nota, Onur Basak, Hans C Clevers, Perry D Moerland, Derk Amsen, René A W van Lier
No abstract text is available yet for this article.
January 19, 2017: Nature Immunology
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