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Cell Host & Microbe

Sizun Jiang, Hufeng Zhou, Jun Liang, Catherine Gerdt, Chong Wang, Liangru Ke, Stefanie C S Schmidt, Yohei Narita, Yijie Ma, Shuangqi Wang, Tyler Colson, Benjamin Gewurz, Guoliang Li, Elliott Kieff, Bo Zhao
Epstein-Barr virus (EBV) transforms B cells to continuously proliferating lymphoblastoid cell lines (LCLs), which represent an experimental model for EBV-associated cancers. EBV nuclear antigens (EBNAs) and LMP1 are EBV transcriptional regulators that are essential for LCL establishment, proliferation, and survival. Starting with the 3D genome organization map of LCL, we constructed a comprehensive EBV regulome encompassing 1,992 viral/cellular genes and enhancers. Approximately 30% of genes essential for LCL growth were linked to EBV enhancers...
October 11, 2017: Cell Host & Microbe
Nicole Tegtmeyer, Silja Wessler, Vittorio Necchi, Manfred Rohde, Aileen Harrer, Tilman T Rau, Carmen Isabell Asche, Manja Boehm, Holger Loessner, Ceu Figueiredo, Michael Naumann, Ralf Palmisano, Enrico Solcia, Vittorio Ricci, Steffen Backert
The Helicobacter pylori (Hp) type IV secretion system (T4SS) forms needle-like pili, whose binding to the integrin-β1 receptor results in injection of the CagA oncoprotein. However, the apical surface of epithelial cells is exposed to Hp, whereas integrins are basolateral receptors. Hence, the mechanism of CagA delivery into polarized gastric epithelial cells remains enigmatic. Here, we demonstrate that T4SS pilus formation during infection of polarized cells occurs predominantly at basolateral membranes, and not at apical sites...
October 11, 2017: Cell Host & Microbe
Tobias Dallenga, Urska Repnik, Björn Corleis, Jacqueline Eich, Rudolph Reimer, Gareth W Griffiths, Ulrich E Schaible
Neutrophils represent the main infected cell population in the lungs of active tuberculosis patients. Efficient removal of infected and dying neutrophils is required to protect the surrounding tissue from bioactive neutrophil molecules and subsequent pathological sequelae. While the removal of apoptotic M. tuberculosis (Mtb)-infected cells, or efferocytosis, is considered beneficial for host defense, little is known about Mtb-infected necrotic neutrophils. We found that Mtb induces necrosis of human neutrophils in an ESX-1-dependent manner, and neutrophil-produced reactive oxygen species (ROS) drive this necrosis...
October 11, 2017: Cell Host & Microbe
Michal P Wandel, Claudio Pathe, Emma I Werner, Cara J Ellison, Keith B Boyle, Alexander von der Malsburg, John Rohde, Felix Randow
Interferon exposure boosts cell-autonomous immunity for more efficient pathogen control. But how interferon-enhanced immunity protects the cytosol against bacteria and how professionally cytosol-dwelling bacteria avoid clearance are insufficiently understood. Here we demonstrate that the interferon-induced GTPase family of guanylate-binding proteins (GBPs) coats Shigella flexneri in a hierarchical manner reliant on GBP1. GBPs inhibit actin-dependent motility and cell-to-cell spread of bacteria but are antagonized by IpaH9...
October 11, 2017: Cell Host & Microbe
Lewis J Entwistle, Victoria S Pelly, Stephanie M Coomes, Yashaswini Kannan, Jimena Perez-Lloret, Stephanie Czieso, Mariana Silva Dos Santos, James I MacRae, Lucy Collinson, Abdul Sesay, Nikolay Nikolov, Amina Metidji, Helena Helmby, David Y Hui, Mark S Wilson
Immunity to intestinal helminth infections has been well studied, but the mechanism of helminth killing prior to expulsion remains unclear. Here we identify epithelial-cell-derived phospholipase A2 group 1B (PLA2g1B) as a host-derived endogenous anthelmintic. PLA2g1B is elevated in resistant mice and is responsible for killing tissue-embedded larvae. Despite comparable activities of other essential type-2-dependent immune mechanisms, Pla2g1b(-/-) mice failed to expel the intestinal helminths Heligmosomoides polygyrus or Nippostrongylus brasiliensis...
October 11, 2017: Cell Host & Microbe
H-Heinrich Hoffmann, William M Schneider, Vincent A Blomen, Margaret A Scull, Alain Hovnanian, Thijn R Brummelkamp, Charles M Rice
Respiratory and arthropod-borne viral infections are a global threat due to the lack of effective antivirals and vaccines. A potential strategy is to target host proteins required for viruses but non-essential for the host. To identify such proteins, we performed a genome-wide knockout screen in human haploid cells and identified the calcium pump SPCA1. SPCA1 is required by viruses from the Paramyxoviridae, Flaviviridae, and Togaviridae families, including measles, dengue, West Nile, Zika, and chikungunya viruses...
October 11, 2017: Cell Host & Microbe
Samuel L Díaz-Muñoz, Rafael Sanjuán, Stuart West
Viruses are involved in various interactions both within and between infected cells. Social evolution theory offers a conceptual framework for how virus-virus interactions, ranging from conflict to cooperation, have evolved. A critical examination of these interactions could expand our understanding of viruses and be exploited for epidemiological and medical interventions.
October 11, 2017: Cell Host & Microbe
Jennifer M Noto, Richard M Peek
Helicobacter pylori type IV secretion system injects the oncoprotein CagA into epithelial cells to drive carcinogenesis. In this issue of Cell Host & Microbe, Tegtmeyer et al. (2017) show that a secreted bacterial protease disrupts apical-junctional complexes, paving the way for H. pylori to access the basolateral compartment and trigger pathogenesis.
October 11, 2017: Cell Host & Microbe
Noelia Lopez-Montero, Jost Enninga
Guanylate-binding proteins (GBPs) confer protection against intracellular pathogens. In this issue of Cell Host & Microbe, Wandel et al. (2017) report that cytosolic Shigella becomes trapped within a GBP coat that prevents bacterial cell-to-cell spread. However, this defense mechanism is counteracted by the bacterial E3 ubiquitin ligase IpaH9.8.
October 11, 2017: Cell Host & Microbe
Mark Palma, Darine W El-Naccache, William C Gause
The determinants of helminth resistance are not well understood. In this issue of Cell Host & Microbe, Entwistle et al. (2017) provide intriguing evidence that a phospholipase A2 (Pla2gb1) produced by epithelial cells can impair larval development in helminths, providing a novel mechanism contributing to intestinal nematode resistance.
October 11, 2017: Cell Host & Microbe
Sonja M Best, Shelly J Robertson
The cellular tropism of noroviruses in immune-competent hosts remains enigmatic. In recent studies in Cell Host & Microbe and Immunity, Lee et al. (2017) and Tomov et al. (2017) determine that norovirus innate immune evasion enables infection of intestinal epithelial cells, escape from adaptive immunity, virus persistence, and shedding.
October 11, 2017: Cell Host & Microbe
Katya Frazier, Vanessa Leone
Gut microbes impact host metabolism via a multitude of mechanisms, including through host circadian rhythm regulation. How microbes influence host circadian networks remains unclear. Recently, Wang et al. (2017) showed that crosstalk between specific microbial components and innate immune cells tunes epithelial circadian oscillations via Nfil3, modulating lipid uptake and metabolism.
October 11, 2017: Cell Host & Microbe
Fei Yu, He Song, Yanling Wu, So Young Chang, Lili Wang, Wei Li, Binbin Hong, Shuai Xia, Chunyu Wang, Surender Khurana, Yang Feng, Yanping Wang, Zhiwu Sun, Biao He, Dongni Hou, Jody Manischewitz, Lisa R King, Yuanlin Song, Ji-Young Min, Hana Golding, Xinhua Ji, Lu Lu, Shibo Jiang, Dimiter S Dimitrov, Tianlei Ying
The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Å) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA...
October 11, 2017: Cell Host & Microbe
Nathan T Porter, Pablo Canales, Daniel A Peterson, Eric C Martens
Capsular polysaccharides (CPSs) play multiple roles in protecting bacteria from host and environmental factors, and many commensal bacteria can produce multiple capsule types. To better understand the roles of different CPSs in competitive intestinal colonization, we individually expressed the eight different capsules of the human gut symbiont Bacteroides thetaiotaomicron. Certain CPSs were most advantageous in vivo, and increased anti-CPS immunoglobulin A correlated with increased fitness of a strain expressing one particular capsule, CPS5, suggesting that it promotes avoidance of adaptive immunity...
October 11, 2017: Cell Host & Microbe
Sanghyun Lee, Craig B Wilen, Anthony Orvedahl, Broc T McCune, Ki-Wook Kim, Robert C Orchard, Stefan T Peterson, Timothy J Nice, Megan T Baldridge, Herbert W Virgin
Cellular tropism during persistent viral infection is commonly conferred by the interaction of a viral surface protein with a host receptor complex. Norovirus, the leading global cause of gastroenteritis, can be persistently shed during infection, but its in vivo cellular tropism and tropism determinants remain unidentified. Using murine norovirus (MNoV), we determine that a small number of intestinal epithelial cells (IECs) serve as the reservoir for fecal shedding and persistence. The viral non-structural protein NS1, rather than a viral surface protein, determines IEC tropism...
October 11, 2017: Cell Host & Microbe
Lillian J Juttukonda, Evelien T M Berends, Joseph P Zackular, Jessica L Moore, Matthew T Stier, Yaofang Zhang, Jonathan E Schmitz, William N Beavers, Christiaan D Wijers, Benjamin A Gilston, Thomas E Kehl-Fie, James Atkinson, Mary K Washington, R Stokes Peebles, Walter J Chazin, Victor J Torres, Richard M Caprioli, Eric P Skaar
Diet, and specifically dietary metals, can modify the risk of infection. However, the mechanisms by which manganese (Mn), a common dietary supplement, alters infection remain unexplored. We report that dietary Mn levels dictate the outcome of systemic infections caused by Staphylococcus aureus, a leading cause of bacterial endocarditis. Mice fed a high Mn diet display alterations in Mn levels and localization within infected tissues, and S. aureus virulence and infection of the heart are enhanced. Although the canonical mammalian Mn-sequestering protein calprotectin surrounds staphylococcal heart abscesses, calprotectin is not released into the abscess nidus and does not limit Mn in this organ...
October 11, 2017: Cell Host & Microbe
Marisel Sanchez, Stacey L Kolar, Sabrina Müller, Christopher N Reyes, Andrea J Wolf, Chihiro Ogawa, Rajat Singhania, Daniel D De Carvalho, Moshe Arditi, David M Underhill, Gislâine A Martins, George Y Liu
Humans do not usually develop effective immunity to Staphylococcus aureus reinfection. Using a murine model that mimics human infection, we show that lack of protective immunity to S. aureus systemic reinfection is associated with robust interleukin-10 (IL-10) production and impaired protective Th17 responses. In dendritic cell co-culture assays, priming with S. aureus promotes robust T cell proliferation, but limits Th cells polarization and production of IL-1β and other cytokines important for Th1 and Th17 differentiation...
October 11, 2017: Cell Host & Microbe
Aaron L Hecht, Benjamin W Casterline, Vivian M Choi, Juliane Bubeck Wardenburg
Intestinal microbes are recognized for their role in human disease. Enterotoxigenic Bacteroides fragilis (ETBF) has been implicated in inflammatory bowel disease and colorectal cancer; however, colonization alone is insufficient to cause these illnesses. We hypothesized that homeostasis in healthy carriers is maintained by colonic mucus, the major constituent of which is the glycoprotein Muc2. We found that Muc2-deficient mice succumb to lethal disease from ETBF colonization in a B. fragilis toxin (BFT)-dependent manner...
October 11, 2017: Cell Host & Microbe
Luis H Franco, Vidhya R Nair, Caitlyn R Scharn, Ramnik J Xavier, Jose R Torrealba, Michael U Shiloh, Beth Levine
No abstract text is available yet for this article.
September 13, 2017: Cell Host & Microbe
Yinghong Xiao, Igor M Rouzine, Simone Bianco, Ashley Acevedo, Elizabeth Faul Goldstein, Mikhail Farkov, Leonid Brodsky, Raul Andino
No abstract text is available yet for this article.
September 13, 2017: Cell Host & Microbe
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