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Infections in compromised host

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https://www.readbyqxmd.com/read/28538182/targeting-metabolic-reprogramming-by-influenza-infection-for-therapeutic-intervention
#1
Heather S Smallwood, Susu Duan, Marie Morfouace, Svetlana Rezinciuc, Barry L Shulkin, Anang Shelat, Erika E Zink, Sandra Milasta, Resha Bajracharya, Ajayi J Oluwaseum, Martine F Roussel, Douglas R Green, Ljiljana Pasa-Tolic, Paul G Thomas
Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28528445/interindividual-spread-of-herpesviruses
#2
Keith W Jarosinski
Interindividual spread of herpesviruses is essential for the virus life cycle and maintenance in host populations. For most herpesviruses, the virus-host relationship is close, having coevolved over millions of years resulting in comparatively high species specificity. The mechanisms governing interindividual spread or horizontal transmission are very complex, involving conserved herpesviral and cellular proteins during the attachment, entry, replication, and egress processes of infection. Also likely, specific herpesviruses have evolved unique viral and cellular interactions during cospeciation that are dependent on their relationship...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28515317/characterization-of-a-secretory-hydrolase-from-mycobacterium-tuberculosis-sheds-critical-insight-into-host-lipid-utilization-by-m-tuberculosis
#3
Khundrakpam Herojit Singh, Bhavya Jha, Abhisek Dwivedy, Eira Choudhary, Arpitha G N, Anam Ashraf, Nisheeth Agarwal, Bichitra Kumar Biswal
Mycobacterium tuberculosis causes tuberculosis in humans and predominantly infects alveolar macrophages. To survive inside host lesions and to evade immune surveillance, this pathogen has developed many strategies. For example, M. tuberculosis uses host-derived lipids/fatty acids as nutrients for prolonged persistence within hypoxic host microenvironments. M. tuberculosis imports these metabolites through its respective transporters, and in the case of host fatty acids, a pertinent question arises: does M. tuberculosis have the enzyme(s) for cleavage of fatty acids from host lipids? We show herein that a previously uncharacterized membrane-associated M...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515136/loss-of-humoral-and-cellular-immunity-to-invasive-nontyphoidal-salmonella-during-current-or-convalescent-plasmodium-falciparum-infection-in-malawian-children
#4
Tonney S Nyirenda, James T Nyirenda, Dumizulu L Tembo, Janet Storm, Queen Dube, Chisomo L Msefula, Kondwani C Jambo, Henry C Mwandumba, Robert S Heyderman, Melita A Gordon, Wilson L Mandala
Invasive nontyphoidal Salmonella (iNTS) infections are commonly associated with Plasmodium falciparum infections, but the immunologic basis for this linkage is poorly understood. We hypothesized that P. falciparum infection compromises the hosts' humoral and cellular immunity to NTS which increases their susceptibility to iNTS infection. We prospectively recruited children aged between 6 and 60 months at a Community Health Centre in Blantyre, Malawi and allocated them to the following groups; febrile with uncomplicated malaria, febrile malaria-negative, non-febrile malaria-negative...
May 17, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28514692/interferon-%C3%AE-mediates-non-redundant-front-line-antiviral-protection-against-influenza-virus-infection-without-compromising-host-fitness
#5
Ioanna E Galani, Vasiliki Triantafyllia, Evridiki-Evangelia Eleminiadou, Ourania Koltsida, Athanasios Stavropoulos, Maria Manioudaki, Dimitris Thanos, Sean E Doyle, Sergei V Kotenko, Kalliopi Thanopoulou, Evangelos Andreakos
Lambda interferons (IFNλs) or type III IFNs share homology, expression patterns, signaling cascades, and antiviral functions with type I IFNs. This has complicated the unwinding of their unique non-redundant roles. Through the systematic study of influenza virus infection in mice, we herein show that IFNλs are the first IFNs produced that act at the epithelial barrier to suppress initial viral spread without activating inflammation. If infection progresses, type I IFNs come into play to enhance viral resistance and induce pro-inflammatory responses essential for confronting infection but causing immunopathology...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28507070/limited-colonization-undermined-by-inadequate-early-immune-responses-define-the-dynamics-of-decidual-listeriosis
#6
Gabrielle Rizzuto, Elisa Tagliani, Priyanka Manandhar, Adrian Erlebacher, Anna I Bakardjiev
The bacterial pathogen Listeria monocytogenes causes a food-borne systemic disease in pregnant women that can lead to preterm labor, stillbirth, or severe neonatal disease. Colonization of the maternal decidua appears to be an initial step in the maternal component of the disease as well as bacterial transmission to the placenta and fetus. Host-pathogen interactions in the decidua during this early stage of infection remain poorly understood. Here, we assessed the dynamics of L. monocytogenes infection in primary human decidual organ cultures and in the murine decidua in vivo...
May 15, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28490590/the-c-terminus-of-the-herpes-simplex-virus-pul25-protein-is-required-for-release-of-viral-genomes-from-capsids-bound-to-nuclear-pores
#7
Jamie B Huffman, Gina R Daniel, Erik Falck-Pedersen, Alexis Huet, Greg A Smith, James F Conway, Fred L Homa
The herpes simplex virus (HSV) capsid is released into the cytoplasm after fusion of viral and host membranes, whereupon dynein-dependent trafficking along microtubules targets it to the nuclear envelope. Binding of the capsid to the nuclear pore complex (NPC) is mediated by the capsid protein pUL25 and the capsid-tethered tegument protein pUL36. Temperature-sensitive mutants in both pUL25 and pUL36 dock at the NPC but fail to release DNA. The uncoating reaction has been difficult to study due to the rapid release of the genome once the capsid interacts with the nuclear pore...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28485720/herpesvirus-micrornas-for-use-in-gene-therapy-immune-evasion-strategies
#8
REVIEW
S T F Bots, R C Hoeben
Transplantation of allogeneic cells as well as of genetically corrected autologous cells are potent approaches to restore cellular functions in patients suffering from genetic diseases. The recipient's immune responses against non-self-antigens may compromise the survival of the grafted cells. Recipients of the graft may therefore require life-long treatment with immunosuppressive drugs. An alternative approach to reduce graft rejection could involve the use of immune-evasion molecules. Expression of such molecules in cells of the graft may subvert recognition by the host's immune system...
May 9, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28483458/killer-cells-in-atherosclerosis
#9
Tin Kyaw, Peter Tipping, Ban-Hock Toh, Alex Bobik
Cytotoxic lymphocytes (killer cells) play a critical role in host defence mechanisms, protecting against infections and in tumour surveillance. They can also exert detrimental effects in chronic inflammatory disorders and in autoimmune diseases. Tissue cell death and necrosis are prominent features of advanced atherosclerotic lesions including vulnerable/unstable lesions which are largely responsible for most heart attacks and strokes. Evidence for accumulation of killer cells in both human and mouse lesions together with their cytotoxic potential strongly suggest that these cells contribute to cell death and necrosis in lesions leading to vulnerable plaque development and potentially plaque rupture...
May 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28477099/nanomedicine-advances-in-toxoplasmosis-diagnostic-treatment-and-vaccine-applications
#10
REVIEW
João Paulo Assolini, Virginia Márcia Concato, Manoela Daiele Gonçalves, Amanda Cristina Machado Carloto, Ivete Conchon-Costa, Wander Rogério Pavanelli, Francine Nesello Melanda, Idessania Nazareth Costa
Toxoplasmosis is an infectious disease caused by the intracellular parasite Toxoplasma gondii that affects about one third of the world's population. The diagnosis of this disease is carried out by parasite isolation and host antibodies detection. However, the diagnosis presents problems in regard to test sensitivity and specificity. Currently, the most effective T. gondii treatment is a combination of pyrimethamine and sulfadiazine, although both drugs are toxic to the host. In addition to the problems that compromise the effective diagnosis and treatment of toxoplasmosis, there are no reports or indications of any vaccine capable of fully protecting against this infection...
May 5, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28468880/selective-activation-of-interferon-%C3%AE-signaling-by-zika-virus-ns5-protein
#11
Vidyanath Chaudhary, Kit-San Yuen, Jasper Fuk-Woo Chan, Ching-Ping Chan, Pei-Hui Wang, Jian-Piao Cai, Shuo Zhang, Mifang Liang, Kin-Hang Kok, Chi-Ping Chan, Kwok-Yung Yuen, Dong-Yan Jin
Severe complications of Zika virus (ZIKV) infection might be caused by inflammation. How ZIKV induces pro-inflammatory cytokines is not understood. In this study, we show opposite regulatory effect of ZIKV NS5 protein on interferon (IFN) signaling. Whereas ZIKV and its NS5 protein were potent suppressors of type I and type III IFN signaling, they were found to activate IFN-γ signaling. Inversely, IFN-γ augmented ZIKV replication. NS5 interacted with STAT2 and targeted it for ubiquitination and degradation, but had no influence on STAT1 stability or nuclear translocation...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28464218/granulocytic-myeloid-derived-suppressor-cells-from-human-cord-blood-modulate-t-helper-cell-response-towards-an-anti-inflammatory-phenotype
#12
Natascha Köstlin, Margit Vogelmann, Bärbel Spring, Julian Schwarz, Judith Feucht, Christoph Härtel, Thorsten W Orlikowsky, Christian F Poets, Christian Gille
Infections are a leading cause of perinatal morbidity and mortality. The outstandingly high susceptibility to infections early in life is mainly attributable to the compromised state of the neonatal immune system. One important difference to the adult immune system is a bias towards T helper (Th) 2-responses in newborns. However, mechanisms regulating neonatal T-cell responses are yet incompletely understood. Granulocytic myeloid-derived suppressor cells (GR-MDSC) are myeloid cells with a granulocytic phenotype that suppress various functions of other immune cells and accumulate under physiological conditions during pregnancy in maternal and foetal blood...
May 2, 2017: Immunology
https://www.readbyqxmd.com/read/28454742/consequences-of-epithelial-inflammasome-activation-by-bacterial-pathogens
#13
REVIEW
Mikael E Sellin, Anna A Müller, Wolf-Dietrich Hardt
Inflammasome signaling impinges on the activation of inflammatory caspases (i.e., caspase-1 and caspase-4/5/11) and endows host cells with a sentinel system to sense microbial intrusion and thereby initiate appropriate immune responses. Lately, it has become evident that mammalian inflammasome-dependent responses to infection are not confined solely to cells of hematopoietic origin. Epithelial cells that line the body's mucosal surfaces use inflammasome signaling to sense and counteract pathogenic microorganisms that compromise barrier integrity...
April 25, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28453484/can-better-management-of-periodontal-disease-delay-the-onset-and-progression-of-alzheimer-s-disease
#14
Alice Harding, Sarita Robinson, StJohn Crean, Sim K Singhrao
A risk factor relationship exists between periodontal disease and Alzheimer's disease (AD) via tooth loss, and improved memory following dental intervention. This links the microbial contribution from indigenous oral periodontal pathogens to the manifestation of chronic conditions, such as AD. Here, we use Porphyromonas gingivalis infection to illustrate its effect on mental health. P. gingivalis infection, in its primary sub-gingival niche, can cause polymicrobial synergy and dysbiosis. Dysbiosis describes the residency of select commensals from the oral cavity following co-aggregation around the dominant keystone pathogen, such as P...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28447887/cyclopiazonic-acid-is-a-pathogenicity-factor-for-aspergillus-flavus-and-a-promising-target-for-screening-germplasm-for-ear-rot-resistance
#15
Subbaiah C Chalivendra, Catherine DeRobertis, Perng-Kuang Chang, Kenneth E Damann
Aspergillus flavus, an opportunistic pathogen, contaminates maize and other key crops with carcinogenic aflatoxins (AFs). Besides AFs, A. flavus makes many more secondary metabolites (SMs) whose toxicity in insects or vertebrates has been studied. However, the role of SMs in the invasion of plant hosts by A. flavus remains to be investigated. Cyclopiazonic acid (CPA), a neurotoxic SM made by A. flavus, is a nanomolar inhibitor of endoplasmic reticulum calcium ATPases (ECAs) and a potent inducer of cell death in plants...
May 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28424283/simian-immunodeficiency-virus-targeting-of-cxcr3-cd4-t-cells-in-secondary-lymphoid-organs-is-associated-with-robust-cxcl10-expression-in-monocyte-macrophage-subsets
#16
Masayuki Fujino, Hirotaka Sato, Tomotaka Okamura, Akihiko Uda, Satoshi Takeda, Nursarat Ahmed, Shigeyuki Shichino, Teiichiro Shiino, Yohei Saito, Satoru Watanabe, Chie Sugimoto, Marcelo Kuroda, Manabu Ato, Yoshiyuki Nagai, Shuji Izumo, Kouji Matsushima, Masaaki Miyazawa, Aftab A Ansari, Francois Villinger, Kazuyasu Mori
Glycosylation of Env defines pathogenic properties of SIV. We previously demonstrated that pathogenic SIVmac239 and live-attenuated, quintuple deglycosylated Env mutant (Δ5G) target CD4(+) T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4(+) T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012). Herein, we studied the host responses relevant to SIV targeting of CXCR3(+)CCR5(+) CD4(+) T cells in SLOs...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28424239/aim2-inflammasome-is-critical-for-influenza-induced-lung-injury-and-mortality
#17
Hongbo Zhang, Jiadi Luo, John F Alcorn, Kong Chen, Songqing Fan, Joseph Pilewski, Aizhong Liu, Wei Chen, Jay K Kolls, Jieru Wang
The absent in melanoma 2 (AIM2) inflammasome plays an important role in many viral and bacterial infections, but very little is known about its role in RNA virus infection, including influenza A virus (IAV). In this study, we have designed in vivo and in vitro studies to determine the role of AIM2 in infections with lethal doses of IAVs A/PR8/34 and A/California/07/09. In wild-type mice, IAV infection enhanced AIM2 expression, induced dsDNA release, and stimulated caspase-1 activation and release of cleaved IL-1β in the lung, which was significantly reduced in AIM2-deficient mice...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28416183/inhibition-of-the-in-vitro-growth-of-babesia-bigemina-babesia-caballi-and-theileria-equi-parasites-by-trifluralin-analogues
#18
Marta G Silva, Donald P Knowles, Sandra Antunes, Ana Domingos, Maria A Esteves, Carlos E Suarez
Bovine and equine babesiosis caused by Babesia bovis, Babesia bigemina and Babesia caballi, along with equine theileriosis caused by Theileria equi are global tick-borne hemoprotozoan diseases characterized by fever, anemia, weight losses and abortions. A common feature of these diseases are transition from acute to chronic phases, in which parasites may persist in the hosts for life. Antiprotozoal drugs are important for managing infection and disease. Previous research demonstrated that trifluralin analogues, designated (TFLAs) 1-15, which specifically bind to regions of alpha-tubulin protein in plants and protozoan parasites, have the ability to inhibit the in vitro growth of B...
April 10, 2017: Ticks and Tick-borne Diseases
https://www.readbyqxmd.com/read/28391509/changes-in-environmental-conditions-modify-infection-kinetics-of-dairy-phages
#19
Delfina Zaburlin, Andrea Quiberoni, Diego Mercanti
Latent period, burst time, and burst size, kinetic parameters of phage infection characteristic of a given phage/host system, have been measured for a wide variety of lactic acid bacteria. However, most studies to date were conducted in optimal growth conditions of host bacteria and did not consider variations due to changes in external factors. In this work, we determined the effect of temperature, pH, and starvation on kinetic parameters of phages infecting Lactobacillus paracasei, Lactobacillus plantarum, and Leuconostoc mesenteroides...
April 8, 2017: Food and Environmental Virology
https://www.readbyqxmd.com/read/28391495/boric-acid-inhibition-of-trichophyton-rubrum-growth-and-conidia-formation
#20
Martin Schmidt
Trichophyton rubrum is a common human dermatophyte that is the causative agent of 80-93% of fungal infections of the skin and nails. While dermatophyte infections in healthy people are easily treatable with over-the-counter medications, such infections pose a higher risk for patients with compromised immune function and impaired regenerative potential. The efficacy of boric acid (BA) for the treatment of vaginal yeast infections prompted an investigation of the effect of BA on growth and morphology of T. rubrum...
April 8, 2017: Biological Trace Element Research
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