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Sterile immunity

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https://www.readbyqxmd.com/read/28087948/regulation-of-immunity-to-tuberculosis
#1
Susanna Brighenti, Diane J Ordway
Immunity against Mycobacterium tuberculosis requires a balance between adaptive immune responses to constrain bacterial replication and the prevention of potentially damaging immune activation. Regulatory T (Treg) cells express the transcription factor Foxp3+ and constitute an essential counterbalance of inflammatory Th1 responses and are required to maintain immune homeostasis. The first reports describing the presence of Foxp3-expressing CD4+ Treg cells in tuberculosis (TB) emerged in 2006. Different Treg cell subsets, most likely specialized for different tissues and microenvironments, have been shown to expand in both human TB and animal models of TB...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28077655/expression-of-ifnlr1-on-intestinal-epithelial-cells-is-critical-to-the-antiviral-effects-of-ifn-lambda-against-norovirus-and-reovirus
#2
Megan T Baldridge, Sanghyun Lee, Judy J Brown, Nicole McAllister, Kelly Urbanek, Terence S Dermody, Timothy J Nice, Herbert W Virgin
: Interferon-lambda (IFN-λ) has potent antiviral effects against multiple enteric viral pathogens, including norovirus and rotavirus, in both preventing and curing infection. Because the intestine includes a diverse array of cell types, however, the cell(s) upon which IFN-λ acts to exert its antiviral effects are unclear. Here, we sought to identify IFN-λ responsive cells by generation of mice with lineage-specific deletion of the receptor for IFN-λ, Ifnlr1 We found that expression of IFNLR1 on intestinal epithelial cells (IECs) in the small intestine and colon is required for enteric IFN-λ antiviral activity...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077589/trimethoprim-sulfamethoxazole-prophylaxis-during-live-malaria-sporozoite-immunization-induces-long-lived-homologous-and-heterologous-protective-immunity-against-sporozoite-challenge
#3
Charlotte V Hobbs, Charles Anderson, Jillian Neal, Tejram Sahu, Solomon Conteh, Tatiana Voza, Jean Langhorne, William Borkowsky, Patrick E Duffy
Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used in malaria-endemic areas in human immunodeficiency virus (HIV)-infected children and HIV-uninfected, HIV-exposed children as opportunistic infection prophylaxis. Despite the known effects that TMP-SMX has in reducing clinical malaria, its impact on development of malaria-specific immunity in these children remains poorly understood. Using rodent malaria models, we previously showed that TMP-SMX, at prophylactic doses, can arrest liver stage development of malaria parasites and speculated that TMP-SMX prophylaxis during repeated malaria exposures would induce protective long-lived sterile immunity targeting pre-erythrocytic stage parasites in mice...
January 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28068953/pregnant-human-peripheral-leukocyte-migration-during-several-late-pregnancy-clinical-conditions-a-cross-sectional-observational-study
#4
Jun Takeda, Xin Fang, David M Olson
BACKGROUND: Parturition at term and preterm is characterized by sterile inflammatory processes occurring in the absence of infection whereby peripheral leukocytes infiltrate gestational tissues in response to chemotactic signals. In response to a homing signal, recruited leukocytes undergo diapedesis and extravasate through capillaries, migrating into stromal tissue. There they interact with resident immune and stromal cells to produce a mixture of matrix metalloproteinases, prostaglandins and cytokines including interleukin-1β (IL-1β) and IL-6 that in turn transform the uterus from pregnancy to parturition...
January 10, 2017: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/28064547/a-systematic-approach-to-autoinflammatory-syndromes-a-spelling-booklet-for-the-beginner
#5
Donato Rigante
Hallmark of autoinflammatory syndromes (AIS) is the periodic recurrence of "sterile" inflammatory attacks characterized by fever and organ- or tissue-specific inflammation. Basic research projects over the last two decades have boosted our understanding of pathological pathways, mainly involving interleukin (IL)-1 biosynthesis, and also revealed that their dysregulation results from genetically-heterogeneous inborn errors of innate immunity and leads to multiple inflammatory phenotypes. Starting from the evidence of poor response to IL-1 inhibitors of some patients with multi-organ inflammation, further research studies have disclosed a crucial role for nuclear factor (NF)-κB and type I interferon (IFN) in specific AIS...
January 9, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28053159/complete-attenuation-of-genetically-engineered-plasmodium-falciparum-sporozoites-in-human-subjects
#6
James G Kublin, Sebastian A Mikolajczak, Brandon K Sack, Matt E Fishbaugher, Annette Seilie, Lisa Shelton, Tracie VonGoedert, Melike Firat, Sara Magee, Emma Fritzen, Will Betz, Heather S Kain, Dorender A Dankwa, Ryan W J Steel, Ashley M Vaughan, D Noah Sather, Sean C Murphy, Stefan H I Kappe
Immunization of humans with whole sporozoites confers complete, sterilizing immunity against malaria infection. However, achieving consistent safety while maintaining immunogenicity of whole parasite vaccines remains a formidable challenge. We generated a genetically attenuated Plasmodium falciparum (Pf) malaria parasite by deleting three genes expressed in the pre-erythrocytic stage (Pf p52(-)/p36(-)/sap1(-)). We then tested the safety and immunogenicity of the genetically engineered (Pf GAP3KO) sporozoites in human volunteers...
January 4, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28052076/diet-matters-endotoxin-in-the-diet-impacts-the-level-of-allergic-sensitization-in-germ-free-mice
#7
Martin Schwarzer, Dagmar Srutkova, Petra Hermanova, Francois Leulier, Hana Kozakova, Irma Schabussova
Germ-free animals have been used to define the vital role of commensal bacteria on the maturation of the host immune system. However, the role of bacterial residues in diet in this setting is poorly understood. Here we investigated the effect of bacterial contamination in sterile diet on the level of allergic sensitization in germ-free mice. Sterile grain-based diets ST1 and R03 were tested for the level of bacterial contamination. ST1 contained higher amount of bacterial DNA, approximately ten times more endotoxin, and induced higher, TLR4-dependent, cytokine production in dendritic cells compared to R03...
2017: PloS One
https://www.readbyqxmd.com/read/28049259/relationship-of-aging-and-nutritional-status-to-innate-immunity-in-tube-fed-bedridden-patients
#8
Yoshiaki Takeuchi, Tomoe Tashiro, Takuya Yamamura, Seiichiro Takahashi, Kozo Katayose, Shin Kohga, Mitsunori Takase, Michio Imawari
BACKGROUND AND OBJECTIVES: Aging and malnutrition are known to influence immune functions. The aim of this study was to investigate the relationship of aging and malnutrition to innate immune functions in tube-fed bedridden patients. METHODS AND STUDY DESIGN: A cross-sectional survey was performed in 71 tube-fed bedridden patients aged 50-95 years (mean age±SD, 80.2±8.5 years) with serum albumin concentrations between 2.5 and 3.5 g/dL. We evaluated associations of age and nutritional variables with natural-killer cell activity, neutrophilphagocytic activity, and neutrophil-sterilizing activity...
January 2017: Asia Pacific Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28038868/marek-s-disease-vaccines-current-status-and-strategies-for-improvement-and-development-of-vector-vaccines
#9
Sanjay M Reddy, Yoshihiro Izumiya, Blanca Lupiani
Marek's disease (MD) is a lymphoproliferative viral disease of chickens, which has been controlled through vaccination since 1969. MD vaccines protect against tumors but do not provide sterilizing immunity, and thus it is generally believed that their use has contributed to increase virulence of field strains with the ability to cause MD in vaccinated chickens. Traditional methods of developing vaccines, like cell culture attenuation, have proved unsuccessful for the development of improved vaccines to protect against highly virulent MD virus (MDV) field strains...
November 24, 2016: Veterinary Microbiology
https://www.readbyqxmd.com/read/28034467/maternal-health-and-the-placental-microbiome
#10
REVIEW
Elise Pelzer, Luisa F Gomez-Arango, Helen L Barrett, Marloes Dekker Nitert
Over the past decade, the role of the microbiome in regulating metabolism, immune function and behavior in humans has become apparent. It has become clear that the placenta is not a sterile organ, but rather has its own endogenous microbiome. The composition of the placental microbiome is distinct from that of the vagina and has been reported to resemble the oral microbiome. Compared to the gut microbiome, the placental microbiome exhibits limited microbial diversity. This review will focus on the current understanding of the placental microbiota in normal healthy pregnancy and also in disease states including preterm birth, chorioamnionitis and maternal conditions such as obesity, gestational diabetes mellitus and preeclampsia...
December 2, 2016: Placenta
https://www.readbyqxmd.com/read/28031267/assessment-of-the-plasmodium-falciparum-pre-erythrocytic-antigen-uis3-as-a-potential-candidate-for-a-malaria-vaccine
#11
Rhea J Longley, Benedict R Halbroth, Ahmed M Salman, Katie J Ewer, Susanne H Hodgson, Chris J Janse, Shahid M Khan, Adrian V S Hill, Alexandra J Spencer
Efforts are currently underway to improve the efficacy of sub-unit malaria vaccines through assessment of new adjuvants, vaccination platforms and antigens. In this study, we further assess the antigen P. falciparum (Pf) upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3 was expressed in the viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) and used to immunize mice in a prime-boost regimen. We previously demonstrated that this regimen could provide partial protection against challenge with chimeric P...
December 28, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/28028710/restoring-ovarian-endocrine-function-with-encapsulated-ovarian-allograft-in-immune-competent-mice
#12
Anu David, James Ronald Day, Alexa Leigh Cichon, Adam Lefferts, Marilia Cascalho, Ariella Shikanov
Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscle wasting, accelerated cardiovascular diseases and a vast array of other health and developmental problems...
December 27, 2016: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28028291/contaminated-milk-is-a-common-cause-of-necrotising-enterocolitis-a-hypothesis
#13
N Y Boo
Necrotising enterocolitis (NEC) is the most commonly acquired gastrointestinal disease of neonates, particularly the very preterm (gestation <32 weeks) and/or very low birth weight (<1500g). It is associated with high morbidity and mortality. Despite improvement in neonatal care and increased use of expressed breast milk (EBM), the incidence remains high in many neonatal intensive care units (NICU), and even shows increasing trend in some countries. Numerous studies have pointed to the infective nature of NEC...
December 2016: Malaysian Journal of Pathology
https://www.readbyqxmd.com/read/28026884/making-a-queen-an-epigenetic-analysis-of-the-robustness-of-the-honey-bee-apis-mellifera-queen-developmental-pathway
#14
Xu Jiang He, Lin Bin Zhou, Qi Zhong Pan, Andrew B Barron, Wei Yu Yan, Zhi Jiang Zeng
Specialised castes are considered a key reason for the evolutionary and ecological success of the social insect lifestyle. The most essential caste distinction is between the fertile queen and the sterile workers. Honey bee (Apis mellifera) workers and queens are not genetically distinct, rather these different phenotypes are the result of epigenetically regulated divergent developmental pathways. This is an important phenomenon in understanding the evolution of social insect societies. Here we studied the genomic regulation of the worker and queen developmental pathways, and the robustness of the pathways by transplanting eggs or young larvae to queen cells...
December 27, 2016: Molecular Ecology
https://www.readbyqxmd.com/read/28009536/leucine-protects-against-skeletal-muscle-atrophy-in-lipopolysaccharide-challenged-rats
#15
Jin Wan, Daiwen Chen, Bing Yu, Yuheng Luo, Xiangbing Mao, Ping Zheng, Jie Yu, Junqiu Luo, Jun He
Skeletal muscle atrophy is a decrease in muscle mass that occurs when protein degradation exceeds protein synthesis. Leucine (Leu), an essential branched-chain amino acid in animal nutrition, regulates skeletal muscle protein metabolism. Two experiments were conducted to evaluate whether Leu could alleviate lipopolysaccharide (LPS)-induced skeletal muscle wasting by modulating skeletal muscle protein synthesis and degradation. A total of 24 rats were randomly allocated into three groups (n = 8): (1) non-challenged control; (2) LPS-challenged control; and (3) LPS +3...
December 23, 2016: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28004802/targeting-dendritic-cells-to-accelerate-t-cell-activation-overcomes-a-bottleneck-in-tuberculosis-vaccine-efficacy
#16
Kristin L Griffiths, Mushtaq Ahmed, Shibali Das, Radha Gopal, William Horne, Terry D Connell, Kelly D Moynihan, Jay K Kolls, Darrell J Irvine, Maxim N Artyomov, Javier Rangel-Moreno, Shabaana A Khader
The development of a tuberculosis (TB) vaccine that induces sterilizing immunity to Mycobacterium tuberculosis infection has been elusive. Absence of sterilizing immunity induced by TB vaccines may be due to delayed activation of mucosal dendritic cells (DCs), and subsequent delay in antigen presentation and activation of vaccine-induced CD4(+) T-cell responses. Here we show that pulmonary delivery of activated M. tuberculosis antigen-primed DCs into vaccinated mice, at the time of M. tuberculosis exposure, can overcome the delay in accumulation of vaccine-induced CD4(+) T-cell responses...
December 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/27997340/specific-memory-b-cell-response-and-participation-of-cd4-central-and-effector-memory-t-cells-in-mice-immunized-with-liposome-encapsulated-recombinant-ne-protein-based-hepatitis-e-vaccine-candidate
#17
Shruti P Kulkarni, Subrat Thanapati, Vidya A Arankalle, Anuradha S Tripathy
BACKGROUND: Liposome encapsulated neutralizing epitope protein of Hepatitis E virus (HEV), rNEp, our Hepatitis E vaccine candidate, was shown to be immunogenic and safe in pregnant and non-pregnant mice and yielded sterilizing immunity in rhesus monkeys. METHODS: The current study in Balb/c mice assessed the levels and persistence of anti-HEV IgG antibodies by ELISA, frequencies of B, memory B, T and memory T cells by flow cytometry and HEV-specific IgG secreting memory B cells by ELISPOT till 420days post immunization (PI) with 5?g rNEp encapsulated in liposome based adjuvant (2 doses, 4weeks apart)...
November 21, 2016: Vaccine
https://www.readbyqxmd.com/read/27994152/disrupting-the-blood-brain-barrier-by-focused-ultrasound-induces-sterile-inflammation
#18
Zsofia I Kovacs, Saejeong Kim, Neekita Jikaria, Farhan Qureshi, Blerta Milo, Bobbi K Lewis, Michele Bresler, Scott R Burks, Joseph A Frank
MRI-guided pulsed focused ultrasound (pFUS) combined with systemic infusion of ultrasound contrast agent microbubbles (MB) causes localized blood-brain barrier (BBB) disruption that is currently being advocated for increasing drug or gene delivery in neurological diseases. The mechanical acoustic cavitation effects of opening the BBB by low-intensity pFUS+MB, as evidenced by contrast-enhanced MRI, resulted in an immediate damage-associated molecular pattern (DAMP) response including elevations in heat-shock protein 70, IL-1, IL-18, and TNFα indicative of a sterile inflammatory response (SIR) in the parenchyma...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27989959/warm-ischemia-time-dependent-variation-in-liver-damage-inflammation-and-function-in-hepatic-ischemia-reperfusion-injury
#19
Pim B Olthof, Rowan F van Golen, Ben Meijer, Adriaan A van Beek, Roelof J Bennink, Joanne Verheij, Thomas M van Gulik, Michal Heger
BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is characterized by hepatocellular damage, sterile inflammation, and compromised postoperative liver function. Generally used mouse I/R models are too severe and poorly reflect the clinical injury profile. The aim was to establish a mouse I/R model with better translatability using hepatocellular injury, liver function, and innate immune parameters as endpoints. METHODS: Mice (C57Bl/6J) were subjected to sham surgery, 30min, or 60min of partial hepatic ischemia...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27981604/malondialdehyde-epitopes-are-sterile-mediators-of-hepatic-inflammation-in-hypercholesterolemic-mice
#20
Clara Jana-Lui Busch, Tim Hendrikx, David Weismann, Sven Jäckel, Sofie M A Walenbergh, André F Rendeiro, Juliane Weißer, Florian Puhm, Anastasiya Hladik, Laura Göderle, Nikolina Papac-Milicevic, Gerald Haas, Vincent Millischer, Saravanan Subramaniam, Sylvia Knapp, Keiryn L Bennett, Christoph Bock, Christoph Reinhardt, Ronit Shiri-Sverdlov, Christoph J Binder
BACKGROUND AND RATIONALE: Diet-related health issues such as non-alcoholic fatty liver disease and cardiovascular disorders are known to have a major inflammatory component. However, the exact pathways linking diet-induced changes e.g. hyperlipidemia, and the ensuing inflammation have remained elusive so far. MAIN RESULTS: We identified biological processes related to innate immunity and oxidative stress as prime response pathways in livers of Ldlr(-/-) mice on Western-type diet using RNA sequencing and in silico functional analyses of transcriptome data...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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