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Cell Host & Microbe

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https://www.readbyqxmd.com/read/28618273/sting-requires-the-adaptor-trif-to-trigger-innate-immune-responses-to-microbial-infection
#1
Xin Wang, Tanmay Majumdar, Patricia Kessler, Evgeny Ozhegov, Ying Zhang, Saurabh Chattopadhyay, Sailen Barik, Ganes C Sen
No abstract text is available yet for this article.
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618272/shigella-sonnei-encodes-a-functional-t6ss-used-for-interbacterial-competition-and-niche-occupancy
#2
Mark C Anderson, Pascale Vonaesch, Azadeh Saffarian, Benoit S Marteyn, Philippe J Sansonetti
Shigella is a leading cause of dysentery worldwide, with the majority of infections caused by two subgroups, S. flexneri and S. sonnei. Although S. flexneri has been highly prevalent in low-income countries, global development has brought an increase in S. sonnei at the expense of S. flexneri. However, the mechanisms behind this shift are not understood. Here we report that S. sonnei, but not S. flexneri, encodes a type VI secretion system (T6SS) that provides a competitive advantage in the gut. S. sonnei competes against E...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618271/lck-hck-fgr-mediated-tyrosine-phosphorylation-negatively-regulates-tbk1-to-restrain-innate-antiviral-responses
#3
Shengduo Liu, Shasha Chen, Xinran Li, Shiying Wu, Qian Zhang, Qiuheng Jin, Lin Hu, Ruyuan Zhou, Zhengyang Yu, Fansen Meng, Siwen Wang, Yaowei Huang, Sheng Ye, Li Shen, Zongping Xia, Jian Zou, Xin-Hua Feng, Pinglong Xu
Cytosolic nucleic acid sensing elicits interferon production for primary antiviral defense through cascades controlled by protein ubiquitination and Ser/Thr phosphorylation. Here we show that TBK1, a core kinase of antiviral pathways, is inhibited by tyrosine phosphorylation. The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation. Accordingly, antiviral sensing and resistance were substantially enhanced in Lck/Hck/Fgr triple knockout cells and ectopic expression of Lck/Hck/Fgr dampened the antiviral defense in cells and zebrafish...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618270/diversity-of-functionally-permissive-sequences-in-the-receptor-binding-site-of-influenza-hemagglutinin
#4
Nicholas C Wu, Jia Xie, Tianqing Zheng, Corwin M Nycholat, Geramie Grande, James C Paulson, Richard A Lerner, Ian A Wilson
Influenza A virus hemagglutinin (HA) initiates viral entry by engaging host receptor sialylated glycans via its receptor-binding site (RBS). The amino acid sequence of the RBS naturally varies across avian and human influenza virus subtypes and is also evolvable. However, functional sequence diversity in the RBS has not been fully explored. Here, we performed a large-scale mutational analysis of the RBS of A/WSN/33 (H1N1) and A/Hong Kong/1/1968 (H3N2) HAs. Many replication-competent mutants not yet observed in nature were identified, including some that could escape from an RBS-targeted broadly neutralizing antibody...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618269/red-blood-cell-invasion-by-the-malaria-parasite-is-coordinated-by-the-pfap2-i-transcription-factor
#5
Joana Mendonca Santos, Gabrielle Josling, Philipp Ross, Preeti Joshi, Lindsey Orchard, Tracey Campbell, Ariel Schieler, Ileana M Cristea, Manuel Llinás
Obligate intracellular parasites must efficiently invade host cells in order to mature and be transmitted. For the malaria parasite Plasmodium falciparum, invasion of host red blood cells (RBCs) is essential. Here we describe a parasite-specific transcription factor PfAP2-I, belonging to the Apicomplexan AP2 (ApiAP2) family, that is responsible for regulating the expression of genes involved in RBC invasion. Our genome-wide analysis by ChIP-seq shows that PfAP2-I interacts with a specific DNA motif in the promoters of target genes...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618268/antigen-availability-shapes-t-cell-differentiation-and-function-during-tuberculosis
#6
Albanus O Moguche, Munyaradzi Musvosvi, Adam Penn-Nicholson, Courtney R Plumlee, Helen Mearns, Hennie Geldenhuys, Erica Smit, Deborah Abrahams, Virginie Rozot, One Dintwe, Søren T Hoff, Ingrid Kromann, Morten Ruhwald, Peter Bang, Ryan P Larson, Shahin Shafiani, Shuyi Ma, David R Sherman, Alessandro Sette, Cecilia S Lindestam Arlehamn, Denise M McKinney, Holden Maecker, Willem A Hanekom, Mark Hatherill, Peter Andersen, Thomas J Scriba, Kevin B Urdahl
CD4 T cells are critical for protective immunity against Mycobacterium tuberculosis (Mtb), the cause of tuberculosis (TB). Yet to date, TB vaccine candidates that boost antigen-specific CD4 T cells have conferred little or no protection. Here we examined CD4 T cell responses to two leading TB vaccine antigens, ESAT-6 and Ag85B, in Mtb-infected mice and in vaccinated humans with and without underlying Mtb infection. In both species, Mtb infection drove ESAT-6-specific T cells to be more differentiated than Ag85B-specific T cells...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618267/enhancement-of-ifn%C3%AE-production-by-distinct-commensals-ameliorates-salmonella-induced-disease
#7
Sophie Thiemann, Nathiana Smit, Urmi Roy, Till Robin Lesker, Eric J C Gálvez, Julia Helmecke, Marijana Basic, Andre Bleich, Andrew L Goodman, Ulrich Kalinke, Richard A Flavell, Marc Erhardt, Till Strowig
The microbiota contributes to colonization resistance against invading pathogens by competing for metabolites, producing inhibitory substances, and priming protective immune responses. However, the specific commensal bacteria that promote host resistance and immune-mediated protection remain largely elusive. Using isogenic mouse lines with distinct microbiota profiles, we demonstrate that severity of disease induced by enteric Salmonella Typhimurium infection is strongly modulated by microbiota composition in individual lines...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618266/il-22%C3%A2-upregulates-epithelial-claudin-2-to-drive-diarrhea-and-enteric-pathogen-clearance
#8
Pei-Yun Tsai, Bingkun Zhang, Wei-Qi He, Juan-Min Zha, Matthew A Odenwald, Gurminder Singh, Atsushi Tamura, Le Shen, Anne Sailer, Sunil Yeruva, Wei-Ting Kuo, Yang-Xin Fu, Sachiko Tsukita, Jerrold R Turner
Diarrhea is a host response to enteric pathogens, but its impact on pathogenesis remains poorly defined. By infecting mice with the attaching and effacing bacteria Citrobacter rodentium, we defined the mechanisms and contributions of diarrhea and intestinal barrier loss to host defense. Increased permeability occurred within 2 days of infection and coincided with IL-22-dependent upregulation of the epithelial tight junction protein claudin-2. Permeability increases were limited to small molecules, as expected for the paracellular water and Na(+) channel formed by claudin-2...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618265/making-the-mark-the-role-of-adenosine-modifications-in-the-life-cycle-of-rna-viruses
#9
REVIEW
Sarah R Gonzales-van Horn, Peter Sarnow
Viral epitranscriptomics is a newly emerging field that has identified unique roles for RNA modifications in modulating life cycles of RNA viruses. Despite the observation of a handful of modified viral RNAs five decades ago, very little was known about how these modifications regulate viral life cycles, until recently. Here we review the pro- and anti-viral effects of methyl-6-adenosine in distinct viral life cycles, the role of 2' O-methyl modifications in RNA stability and innate immune sensing, and functions of adenosine to inosine modifications in retroviral life cycles...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618264/unconventional-interrogation-yields-hiv-s-escape-plan
#10
Thomas B Kepler
Chasing HIV-1 across the genotype landscape, unequipped to anticipate its maneuvers, the antibody variable-region genes pursue the virus in futility. In this issue of Cell Host & Microbe, Dingens et al. (2017) exhibit a powerful technology that reveals the escape pathways of HIV-1 and may enable its capture.
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618263/relish-the-thought-and-channel-your-chloride-for-bacterial-clearance-depends-on-it
#11
Amanda J Monahan, Neal Silverman
Macrophage-mediated bacterial clearance relies on phagocytic uptake of the pathogen, subsequent phagolysosomal maturation, and microbial degradation. In this issue of Cell Host & Microbe, Wong et al. (2017) report that a chloride transporter couples phagocytosis and bacterial clearance in an NF-κB-mediated feedforward loop, which is required for sustained pathogen uptake.
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618262/the-helper-t-cell-s-dilemma-in-tuberculosis
#12
Daniel L Barber
Vaccination approaches eliciting strong CD4 T cell responses provide only weak protection from tuberculosis. In this issue of Cell Host & Microbe, Moguche et al. (2017) show that T cells specific for different immunodominant vaccine antigens can fail to protect for opposite reasons, highlighting a major challenge in tuberculosis vaccine design.
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618261/the-making-of-a-pathogen
#13
Kim Lewis, Mariaelena Caboni
Enterococci are opportunistic pathogens, hard to eradicate because of their unusually robust resistance to antibiotics, disinfectants, and desiccation. In recent work, Lebreton et al. (2017) show that traits promoting survival in hospitals were acquired upon adaptation to terrestrial life when Enterococci split from marine ancestors 400 million years ago.
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618260/protectors-of-the-neonatal-gut-clostridia-send-pathogens-packing
#14
Judith Behnsen
Commensal bacteria are known to provide colonization resistance in the gut. But exactly which ones provide this function? In a recent paper in Science, Kim et al. (2017) revealed that Clostridia added to mouse infant gut microbiota are sufficient to limit colonization of pathogenic Enterobacteriaceae.
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28579255/lysosomal-degradation-is-required-for-sustained-phagocytosis-of-bacteria-by-macrophages
#15
Ching-On Wong, Steven Gregory, Hongxiang Hu, Yufang Chao, Victoria E Sepúlveda, Yuchun He, David Li-Kroeger, William E Goldman, Hugo J Bellen, Kartik Venkatachalam
Clearance of bacteria by macrophages involves internalization of the microorganisms into phagosomes, which are then delivered to endolysosomes for enzymatic degradation. These spatiotemporally segregated processes are not known to be functionally coupled. Here, we show that lysosomal degradation of bacteria sustains phagocytic uptake. In Drosophila and mammalian macrophages, lysosomal dysfunction due to loss of the endolysosomal Cl(-) transporter ClC-b/CLCN7 delayed degradation of internalized bacteria. Unexpectedly, defective lysosomal degradation of bacteria also attenuated further phagocytosis, resulting in elevated bacterial load...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28579254/comprehensive-mapping-of-hiv-1-escape-from-a-broadly-neutralizing-antibody
#16
Adam S Dingens, Hugh K Haddox, Julie Overbaugh, Jesse D Bloom
Precisely defining how viral mutations affect HIV's sensitivity to antibodies is vital to develop and evaluate vaccines and antibody immunotherapeutics. Despite great effort, a full map of escape mutants has not been delineated for an anti-HIV antibody. We describe a massively parallel experimental approach to quantify how all single amino acid mutations to HIV Envelope (Env) affect neutralizing antibody sensitivity in the context of replication-competent virus. We apply this approach to PGT151, a broadly neutralizing antibody recognizing a combination of Env residues and glycans...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28552668/%C3%AE-1-integrin-accumulates-in-cystic-fibrosis-luminal-airway-epithelial-membranes-and-decreases-sphingosine-promoting-bacterial-infections
#17
Heike Grassmé, Brian Henry, Regan Ziobro, Katrin Anne Becker, Joachim Riethmüller, Aaron Gardner, Aaron P Seitz, Joerg Steinmann, Stephan Lang, Christopher Ward, Edward H Schuchman, Charles C Caldwell, Markus Kamler, Michael J Edwards, Malcolm Brodlie, Erich Gulbins
Chronic pulmonary colonization with bacterial pathogens, particularly Pseudomonas aeruginosa, is the primary cause of morbidity and mortality in patients with cystic fibrosis (CF). We observed that β1-integrins accumulate on the luminal membrane of upper-airway epithelial cells from mice and humans with CF. β1-integrin accumulation is due to increased ceramide and the formation of ceramide platforms that trap β1-integrins on the luminal pole of bronchial epithelial cells. β1-integrins downregulate acid ceramidase expression, resulting in further accumulation of ceramide and consequent reduction of surface sphingosine, a lipid that kills bacteria...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494245/global-reprogramming-of-host-kinase-signaling-in-response-to-fungal-infection
#18
Aseem Pandey, Sheng Li Ding, Qing-Ming Qin, Rahul Gupta, Gabriel Gomez, Furong Lin, Xuehuan Feng, Luciana Fachini da Costa, Sankar P Chaki, Madhu Katepalli, Elizabeth D Case, Erin J van Schaik, Tabasum Sidiq, Omar Khalaf, Angela Arenas, Koichi S Kobayashi, James E Samuel, Gonzalo M Rivera, Robert C Alaniz, Sing-Hoi Sze, Xiaoning Qian, William J Brown, Allison Rice-Ficht, William K Russell, Thomas A Ficht, Paul de Figueiredo
Cryptococcus neoformans (Cn) is a deadly fungal pathogen whose intracellular lifestyle is important for virulence. Host mechanisms controlling fungal phagocytosis and replication remain obscure. Here, we perform a global phosphoproteomic analysis of the host response to Cryptococcus infection. Our analysis reveals numerous and diverse host proteins that are differentially phosphorylated following fungal ingestion by macrophages, thereby indicating global reprogramming of host kinase signaling. Notably, phagocytosis of the pathogen activates the host autophagy initiation complex (AIC) and the upstream regulatory components LKB1 and AMPKα, which regulate autophagy induction through their kinase activities...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494244/quorum-sensing-attenuates-virulence-in-sodalis-praecaptivus
#19
Shinichiro Enomoto, Abhishek Chari, Adam Larsen Clayton, Colin Dale
Sodalis praecaptivus is a close relative and putative environmental progenitor of the widely distributed, insect-associated, Sodalis-allied symbionts. Here we show that mutant strains of S. praecaptivus that lack genetic components of a quorum-sensing (QS) apparatus have a rapid and potent killing phenotype following microinjection into an insect host. Transcriptomic and genetic analyses indicate that insect killing occurs as a consequence of virulence factors, including insecticidal toxins and enzymes that degrade the insect integument, which are normally repressed by QS at high infection densities...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494243/a-rab20-dependent-membrane-trafficking-pathway-controls-m-%C3%A2-tuberculosis-replication-by-regulating-phagosome-spaciousness-and-integrity
#20
Laura Schnettger, Angela Rodgers, Urska Repnik, Rachel P Lai, Gang Pei, Martijn Verdoes, Robert J Wilkinson, Douglas B Young, Maximiliano G Gutierrez
The intracellular pathogen Mycobacterium tuberculosis (Mtb) lives within phagosomes and also disrupts these organelles to access the cytosol. The host pathways and mechanisms that contribute to maintaining Mtb phagosome integrity have not been investigated. Here, we examined the spatiotemporal dynamics of Mtb-containing phagosomes and identified an interferon-gamma-stimulated and Rab20-dependent membrane trafficking pathway in macrophages that maintains Mtb in spacious proteolytic phagolysosomes. This pathway functions to promote endosomal membrane influx in infected macrophages, and is required to preserve Mtb phagosome integrity and control Mtb replication...
May 10, 2017: Cell Host & Microbe
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