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Cell Host & Microbe

Roshan J Thapa, Justin P Ingram, Katherine B Ragan, Shoko Nogusa, David F Boyd, Asiel A Benitez, Haripriya Sridharan, Rachelle Kosoff, Maria Shubina, Vanessa J Landsteiner, Mark Andrake, Peter Vogel, Luis J Sigal, Benjamin R tenOever, Paul G Thomas, Jason W Upton, Siddharth Balachandran
Influenza A virus (IAV) is an RNA virus that is cytotoxic to most cell types in which it replicates. IAV activates the host kinase RIPK3, which induces cell death via parallel pathways of necroptosis, driven by the pseudokinase MLKL, and apoptosis, dependent on the adaptor proteins RIPK1 and FADD. How IAV activates RIPK3 remains unknown. We report that DAI (ZBP1/DLM-1), previously implicated as a cytoplasmic DNA sensor, is essential for RIPK3 activation by IAV. Upon infection, DAI recognizes IAV genomic RNA, associates with RIPK3, and is required for recruitment of MLKL and RIPK1 to RIPK3...
October 8, 2016: Cell Host & Microbe
Alon Vitenshtein, Yoav Charpak-Amikam, Rachel Yamin, Yoav Bauman, Batya Isaacson, Natan Stein, Orit Berhani, Liat Dassa, Moriya Gamliel, Chamutal Gur, Ariella Glasner, Carlos Gomez, Ronen Ben-Ami, Nir Osherov, Brendan P Cormack, Ofer Mandelboim
Natural killer (NK) cells form an important arm of the innate immune system and function to combat a wide range of invading pathogens, ranging from viruses to bacteria. However, the means by which NK cells accomplish recognition of pathogens with a limited repertoire of receptors remain largely unknown. In the current study, we describe the recognition of an emerging fungal pathogen, Candida glabrata, by the human NK cytotoxic receptor NKp46 and its mouse ortholog, NCR1. Using NCR1 knockout mice, we observed that this receptor-mediated recognition was crucial for controlling C...
October 12, 2016: Cell Host & Microbe
Lei Li, Panya Kim, Liping Yu, Gaihong Cai, She Chen, James R Alfano, Jian-Min Zhou
The Arabidopsis immune receptor FLS2 and co-receptor BAK1 perceive the bacterial flagellin epitope flg22 to activate plant immunity. To prevent this response, phytopathogenic bacteria deploy a repertoire of effector proteins to perturb immune signaling. However, the effector-induced perturbation is often sensed by the host, triggering another layer of immunity. We report that the Pseudomonas syringae effector HopB1 acts as a protease to cleave immune-activated BAK1. Prior to activation, HopB1 constitutively interacts with FLS2...
October 12, 2016: Cell Host & Microbe
Damien Keogh, Wei Hong Tay, Yao Yong Ho, Jennifer L Dale, Siyi Chen, Shivshankar Umashankar, Rohan B H Williams, Swaine L Chen, Gary M Dunny, Kimberly A Kline
Enterococcus faecalis is frequently associated with polymicrobial infections of the urinary tract, indwelling catheters, and surgical wound sites. E. faecalis co-exists with Escherichia coli and other pathogens in wound infections, but mechanisms that govern polymicrobial colonization and pathogenesis are poorly defined. During infection, bacteria must overcome multiple host defenses, including nutrient iron limitation, to persist and cause disease. In this study, we investigated the contribution of E. faecalis to mixed-species infection when iron availability is restricted...
October 12, 2016: Cell Host & Microbe
Dalit Talmi-Frank, Zeev Altboum, Inna Solomonov, Yael Udi, Diego Adhemar Jaitin, Mordehay Klepfish, Eyal David, Alina Zhuravlev, Hadas Keren-Shaul, Deborah R Winter, Irit Gat-Viks, Michal Mandelboim, Tamar Ziv, Ido Amit, Irit Sagi
Mounting an effective immune response, while also protecting tissue integrity, is critical for host survival. We used a combined genomic and proteomic approach to investigate the role of extracellular matrix (ECM) proteolysis in achieving this balance in the lung during influenza virus infection. We identified the membrane-tethered matrix metalloprotease MT1-MMP as a prominent host-ECM-remodeling collagenase in influenza infection. Selective inhibition of MT1-MMP protected the tissue from infection-related structural and compositional tissue damage...
October 12, 2016: Cell Host & Microbe
Shuting Xu, Aurélie Ducroux, Aparna Ponnurangam, Gabrielle Vieyres, Sergej Franz, Mathias Müsken, Thomas Zillinger, Angelina Malassa, Ellen Ewald, Veit Hornung, Winfried Barchet, Susanne Häussler, Thomas Pietschmann, Christine Goffinet
Upon sensing cytoplasmic retroviral DNA in infected cells, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide cGAMP, which activates STING to trigger a type I interferon (IFN) response. We find that membrane fusion-inducing contact between donor cells expressing the HIV envelope (Env) and primary macrophages endogenously expressing the HIV receptor CD4 and coreceptor enable intercellular transfer of cGAMP. This cGAMP exchange results in STING-dependent antiviral IFN responses in target macrophages and protection from HIV infection...
October 12, 2016: Cell Host & Microbe
Kai Dallmeier, Johan Neyts
The Zika emergency calls for urgent countermeasures. Recently, Barrows et al. (2016) and Xu et al. (2016) conducted in vitro anti-ZIKV screens to identify potential therapeutics. The off-label use of drugs that may protect against Zika virus-induced brain damage has, however, to be balanced with their risk during pregnancy.
October 12, 2016: Cell Host & Microbe
P'ng Loke, Yvonne A L Lim
Gut commensals profoundly affect host immunity and intestinal homeostasis, but the impact of commensal eukaryotic protozoans is poorly understood. In a recent Cell paper, Chudnovskiy et al. (2016) identify a commensal protozoan, Tritrichomonas musculis, that can enhance anti-bacterial defenses, but at the cost of increasing intestinal inflammation.
October 12, 2016: Cell Host & Microbe
David Berry
Modification of the intestinal microbiome is an emerging target to improve health and prevent or treat a number of diseases. In this issue of Cell Host & Microbe, Maldonado-Gómez et al. (2016) uncover the basic principles that govern the successful establishment and persistence of an exogenously introduced gut bacterium.
October 12, 2016: Cell Host & Microbe
Jeff H Chang, Javier F Tabima
Phytopathogens have mastered the ability to evade plant innate immunity. In this issue of Cell Host & Microbe, Zhou and colleagues (Li et al., 2016) uncover a strategy whereby a bacterial pathogen disables the plant immune system with such precision as to avoid triggering alarms that could potentially reveal its presence.
October 12, 2016: Cell Host & Microbe
Elizabeth R Hughes, Sebastian E Winter
Many infectious diseases involve polymicrobial infections, which are characterized by synergistic interactions between different microorganisms colonizing a host. In this issue of Cell Host & Microbe, Keogh et al. (2016) show that Enterococcus faecalis promotes Escherichia coli biofilm formation in low-iron conditions, thus facilitating polymicrobial growth.
October 12, 2016: Cell Host & Microbe
Simon J Labrie, Sylvain Moineau
Bacterial genomic islands contain hidden treasures. In this issue of Cell Host & Microbe, Depardieu et al. (2016) found, in one of those islands, an altruistic anti-phage system that is triggered by a phage component and induces a phosphorylation cascade leading to protection of the bacterial population.
October 12, 2016: Cell Host & Microbe
Daniel Sauter, Frank Kirchhoff
IFITMs inhibit various enveloped viral pathogens in vitro, but their relevance in vivo has remained unclear. In this issue of Cell Host & Microbe, Foster et al. (2016) show that IFITMs constitute a barrier to HIV-1 transmission and that escape from adaptive immune responses increases viral sensitivity to IFITM restriction.
October 12, 2016: Cell Host & Microbe
Nicholas L Bayless, Rachel S Greenberg, Tomek Swigut, Joanna Wysocka, Catherine A Blish
Zika virus (ZIKV) infection during pregnancy is linked to microcephaly, which is attributed to infection of developing brain structures. ZIKV infects neural progenitor cells in vitro, though its effects on other developmentally relevant stem cell populations, including cranial neural crest cells (CNCCs), have not been assessed. CNCCs give rise to most cranial bones and exert paracrine effects on the developing brain. Here, we report that CNCCs are productively infected by ZIKV, but not by the related dengue virus...
October 12, 2016: Cell Host & Microbe
María X Maldonado-Gómez, Inés Martínez, Francesca Bottacini, Amy O'Callaghan, Marco Ventura, Douwe van Sinderen, Benjamin Hillmann, Pajau Vangay, Dan Knights, Robert W Hutkins, Jens Walter
Live bacteria (such as probiotics) have long been used to modulate gut microbiota and human physiology, but their colonization is mostly transient. Conceptual understanding of the ecological principles as they apply to exogenously introduced microbes in gut ecosystems is lacking. We find that, when orally administered to humans, Bifidobacterium longum AH1206 stably persists in the gut of 30% of individuals for at least 6 months without causing gastrointestinal symptoms or impacting the composition of the resident gut microbiota...
October 12, 2016: Cell Host & Microbe
C Preston Neff, Matthew E Rhodes, Kathleen L Arnolds, Colm B Collins, Jody Donnelly, Nichole Nusbacher, Paul Jedlicka, Jennifer M Schneider, Martin D McCarter, Michael Shaffer, Sarkis K Mazmanian, Brent E Palmer, Catherine A Lozupone
Zwitterionic capsular polysaccharides (ZPSs) are bacterial products that modulate T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells (Tregs). However, only a few diverse bacteria are known to modulate the host immune system via ZPS. We present a genomic screen for bacteria encoding ZPS molecules. We identify diverse host-associated bacteria, including commensals and pathogens with known anti-inflammatory properties, with the capacity to produce ZPSs. Human mononuclear cells stimulated with lysates from putative ZPS-producing bacteria induce significantly greater IL-10 production and higher proportions of Tregs than lysates from non-ZPS-encoding relatives or a commensal strain of Bacteroides cellulosilyticus in which a putative ZPS biosynthetic operon was genetically disrupted...
October 12, 2016: Cell Host & Microbe
Florence Depardieu, Jean-Philippe Didier, Aude Bernheim, Andrew Sherlock, Henrik Molina, Bertrand Duclos, David Bikard
Organisms from all domains of life are infected by viruses. In eukaryotes, serine/threonine kinases play a central role in antiviral response. Bacteria, however, are not commonly known to use protein phosphorylation as part of their defense against phages. Here we identify Stk2, a staphylococcal serine/threonine kinase that provides efficient immunity against bacteriophages by inducing abortive infection. A phage protein of unknown function activates the Stk2 kinase. This leads to the Stk2-dependent phosphorylation of several proteins involved in translation, global transcription control, cell-cycle control, stress response, DNA topology, DNA repair, and central metabolism...
October 12, 2016: Cell Host & Microbe
Matt S Conover, Ségolène Ruer, Joemar Taganna, Vasilios Kalas, Henri De Greve, Jerome S Pinkner, Karen W Dodson, Han Remaut, Scott J Hultgren
Uropathogenic E. coli (UPEC) is the dominant cause of urinary tract infections, clinically described as cystitis. UPEC express CUP pili, which are extracellular fibers tipped with adhesins that bind mucosal surfaces of the urinary tract. Here we identify the role of the F9/Yde/Fml pilus for UPEC persistence in the inflamed urothelium. The Fml adhesin FmlH binds galactose β1-3 N-acetylgalactosamine found in core-1 and -2 O-glycans. Deletion of fmlH had no effect on UPEC virulence in an acute mouse model of cystitis...
October 12, 2016: Cell Host & Microbe
Toshana L Foster, Harry Wilson, Shilpa S Iyer, Karen Coss, Katie Doores, Sarah Smith, Paul Kellam, Andrés Finzi, Persephone Borrow, Beatrice H Hahn, Stuart J D Neil
Interferon-induced transmembrane proteins (IFITMs) restrict the entry of diverse enveloped viruses through incompletely understood mechanisms. While IFITMs are reported to inhibit HIV-1, their in vivo relevance is unclear. We show that IFITM sensitivity of HIV-1 strains is determined by the co-receptor usage of the viral envelope glycoproteins as well as IFITM subcellular localization within the target cell. Importantly, we find that transmitted founder HIV-1, which establishes de novo infections, is uniquely resistant to the antiviral activity of IFITMs...
October 12, 2016: Cell Host & Microbe
Melissa Kane, Trinity M Zang, Suzannah J Rihn, Fengwen Zhang, Tonya Kueck, Mudathir Alim, John Schoggins, Charles M Rice, Sam J Wilson, Paul D Bieniasz
Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species...
September 14, 2016: Cell Host & Microbe
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