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Cell Host & Microbe

Xin Li, Irina Leonardi, Alexa Semon, Itai Doron, Iris H Gao, Gregory Garbès Putzel, Youngjun Kim, Hiroki Kabata, David Artis, William D Fiers, Amanda E Ramer-Tait, Iliyan D Iliev
Sensing of the gut microbiota, including fungi, regulates mucosal immunity. Whether fungal sensing in the gut can influence immunity at other body sites is unknown. Here we show that fluconazole-induced gut fungal dysbiosis has persistent effects on allergic airway disease in a house dust mite challenge model. Mice with a defined community of bacteria, but lacking intestinal fungi were not susceptible to fluconazole-induced dysbiosis, while colonization with a fungal mixture recapitulated the detrimental effects...
November 20, 2018: Cell Host & Microbe
Céline Pattaroni, Martin L Watzenboeck, Sabrina Schneidegger, Silas Kieser, Nicholas C Wong, Eric Bernasconi, Julie Pernot, Louis Mercier, Sylvia Knapp, Laurent P Nicod, Colin P Marsland, Matthias Roth-Kleiner, Benjamin J Marsland
Crosstalk between immune cells and the microbiota in mucosal tissues can set an individual on a trajectory toward health or disease. Little is known about these early-life events in the human respiratory tract. We examined bacterial colonization and immune system maturation in the lower airways over the first year of life. The lower respiratory tract microbiota forms within the first 2 postnatal months. Within the first weeks, three microbial profiles are evident, broadly distinguished as dysbiotic or diverse, and representing different microbial virulence potentials, including proteolysis of immunoglobulin A (IgA) that is critical for mucosal defense...
November 19, 2018: Cell Host & Microbe
Adam J Fletcher, Marina Vaysburd, Sarah Maslen, Jingwei Zeng, J Mark Skehel, Greg J Towers, Leo C James
TRIM5 is a RING domain E3 ubiquitin ligase with potent antiretroviral function. TRIM5 assembles into a hexagonal lattice on retroviral capsids, causing envelopment of the infectious core. Concomitantly, TRIM5 initiates innate immune signaling and orchestrates disassembly of the viral particle, yet how these antiviral responses are regulated by capsid recognition is unclear. We show that hexagonal assembly triggers N-terminal polyubiquitination of TRIM5 that collectively drives antiviral responses. In uninfected cells, N-terminal monoubiquitination triggers non-productive TRIM5 turnover...
November 13, 2018: Cell Host & Microbe
Kevin M Brown, L David Sibley
Apicomplexan parasites rely on cyclic nucleotide-dependent kinases for host cell infection, yet the mechanisms that control their activation remain unknown. Here we show that an apically localized guanylate cyclase (GC) controls microneme secretion and lytic growth in the model apicomplexan Toxoplasma gondii. Cell-permeable cGMP reversed the block in microneme secretion seen in a knockdown of TgGC, linking its function to production of cGMP. TgGC possesses an N-terminal P-type ATPase domain fused to a C-terminal heterodimeric guanylate cyclase domain, an architecture found only in Apicomplexa and related protists...
November 12, 2018: Cell Host & Microbe
Pan Li, Yifan Wei, Miao Mei, Lei Tang, Lei Sun, Wenze Huang, Jianyu Zhou, Chunlin Zou, Shaojun Zhang, Cheng-Feng Qin, Tao Jiang, Jianfeng Dai, Xu Tan, Qiangfeng Cliff Zhang
Zika virus (ZIKV) strains can be classified into the ancestral African and contemporary Asian lineages, with the latter responsible for recent epidemics associated with neurological conditions. To understand how Asian strains lead to exacerbated disease, a crucial step is identifying genomic variations that affect infectivity and pathogenicity. Here we use two high-throughput sequencing approaches to assess RNA secondary structures and intramolecular RNA-RNA interactions in vivo for the RNA genomes of Asian and African ZIKV lineages...
November 9, 2018: Cell Host & Microbe
Tong Dai, Liming Wu, Shuai Wang, Jing Wang, Feng Xie, Zhengkui Zhang, Xiuwu Fang, Jingxian Li, Pengfei Fang, Fang Li, Ke Jin, Jianfeng Dai, Bing Yang, Fangfang Zhou, Hans van Dam, Dachuan Cai, Huizhe Huang, Long Zhang
Mitochondrial antiviral signaling protein (MAVS) is an adaptor of the innate immune receptor retinoic acid-inducible gene 1 (RIG-I) that links recognition of viral RNA to antiviral signaling. Upon interacting with RIG-I, MAVS undergoes lysine 63-linked poly-ubiquitination by the E3 ligase TRIM31 and subsequently aggregates to activate downstream signaling effectors. We find that the scaffold protein FAF1 forms aggregates that negatively regulate MAVS. FAF1 antagonizes the poly-ubiquitination and aggregation of MAVS by competing with TRIM31 for MAVS association...
November 8, 2018: Cell Host & Microbe
Emma Guerin, Andrey Shkoporov, Stephen R Stockdale, Adam G Clooney, Feargal J Ryan, Thomas D S Sutton, Lorraine A Draper, Enrique Gonzalez-Tortuero, R Paul Ross, Colin Hill
CrAssphages represent the most abundant virus in the human gut microbiota, but the lack of available genome sequences for comparison has kept them enigmatic. Recently, sequence-based classification of distantly related crAss-like phages from multiple environments was reported, leading to a proposed familial-level taxonomic group. Here, we assembled the metagenomic sequencing reads from 702 human fecal virome/phageome samples and analyzed 99 complete circular crAss-like phage genomes and 150 contigs ≥70 kb...
November 14, 2018: Cell Host & Microbe
Yun Teng, Yi Ren, Mohammed Sayed, Xin Hu, Chao Lei, Anil Kumar, Elizabeth Hutchins, Jingyao Mu, Zhongbin Deng, Chao Luo, Kumaran Sundaram, Mukesh K Sriwastva, Lifeng Zhang, Michael Hsieh, Rebecca Reiman, Bodduluri Haribabu, Jun Yan, Venkatakrishna Rao Jala, Donald M Miller, Kendall Van Keuren-Jensen, Michael L Merchant, Craig J McClain, Juw Won Park, Nejat K Egilmez, Huang-Ge Zhang
The gut microbiota can be altered by dietary interventions to prevent and treat various diseases. However, the mechanisms by which food products modulate commensals remain largely unknown. We demonstrate that plant-derived exosome-like nanoparticles (ELNs) are taken up by the gut microbiota and contain RNAs that alter microbiome composition and host physiology. Ginger ELNs (GELNs) are preferentially taken up by Lactobacillaceae in a GELN lipid-dependent manner and contain microRNAs that target various genes in Lactobacillus rhamnosus (LGG)...
November 14, 2018: Cell Host & Microbe
Basel H Abuaita, Tracey L Schultz, Mary X O'Riordan
Pathogenic bacteria taken up into the macrophage phagosome are the target of many anti-microbial mechanisms. Although mitochondria-derived antimicrobial effectors like reactive oxygen species (mROS) aid in bacterial killing, it is unclear how these effectors reach bacteria within the phagosomal lumen. We show here that endoplasmic reticulum stress triggered upon methicillin-resistant Staphylococcus aureus (MRSA) infection induces mROS that are delivered to bacteria-containing phagosomes via mitochondria-derived vesicles (MDVs)...
November 14, 2018: Cell Host & Microbe
Angela M Fowler, William W Tang, Matthew P Young, Anila Mamidi, Karla M Viramontes, Melanie D McCauley, Aaron F Carlin, Robert T Schooley, Jesica Swanstrom, Ralph S Baric, Jennifer Govero, Michael S Diamond, Sujan Shresta
Antibody (Ab)-dependent enhancement can exacerbate dengue virus (DENV) infection due to cross-reactive Abs from an initial DENV infection, facilitating replication of a second DENV. Zika virus (ZIKV) emerged in DENV-endemic areas, raising questions about whether existing immunity could affect these related flaviviruses. We show that mice born with circulating maternal Abs against ZIKV develop severe disease upon DENV infection. Compared with pups of naive mothers, those born to ZIKV-immune mice lacking type I interferon receptor in myeloid cells (LysMCre+ Ifnar1fl/fl ) exhibit heightened disease and viremia upon DENV infection...
November 14, 2018: Cell Host & Microbe
Matthew G Zimmerman, Kendra M Quicke, Justin T O'Neal, Nitin Arora, Deepa Machiah, Lalita Priyamvada, Robert C Kauffman, Emery Register, Oluwaseyi Adekunle, Dominika Swieboda, Erica L Johnson, Sarah Cordes, Lisa Haddad, Rana Chakraborty, Carolyn B Coyne, Jens Wrammert, Mehul S Suthar
Zika virus (ZIKV), which emerged in regions endemic to dengue virus (DENV), is vertically transmitted and results in adverse pregnancy outcomes. Antibodies to DENV can cross-react with ZIKV, but whether these antibodies influence ZIKV vertical transmission remains unclear. Here, we find that DENV antibodies increase ZIKV infection of placental macrophages (Hofbauer cells [HCs]) from 10% to over 80% and enhance infection of human placental explants. ZIKV-anti-DENV antibody complexes increase viral binding and entry into HCs but also result in blunted type I interferon, pro-inflammatory cytokine, and antiviral responses...
November 14, 2018: Cell Host & Microbe
Valerie J Kinchen, Muhammad N Zahid, Andrew I Flyak, Mary G Soliman, Gerald H Learn, Shuyi Wang, Edgar Davidson, Benjamin J Doranz, Stuart C Ray, Andrea L Cox, James E Crowe, Pamela J Bjorkman, George M Shaw, Justin R Bailey
The role that broadly neutralizing antibodies (bNAbs) play in natural clearance of human hepatitis C virus (HCV) infection and the underlying mechanisms remain unknown. Here, we investigate the mechanism by which bNAbs, isolated from two humans who spontaneously cleared HCV infection, contribute to HCV control. Using viral gene sequences amplified from longitudinal plasma of the two subjects, we found that these bNAbs, which target the front layer of the HCV envelope protein E2, neutralized most autologous HCV strains...
November 14, 2018: Cell Host & Microbe
Andrew I Flyak, Stormy Ruiz, Michelle D Colbert, Tiffany Luong, James E Crowe, Justin R Bailey, Pamela J Bjorkman
Hepatitis C virus (HCV) vaccine efforts are hampered by the extensive genetic diversity of HCV envelope glycoproteins E1 and E2. Structures of broadly neutralizing antibodies (bNAbs) (e.g., HEPC3, HEPC74) isolated from individuals who spontaneously cleared HCV infection facilitate immunogen design to elicit antibodies against multiple HCV variants. However, challenges in expressing HCV glycoproteins previously limited bNAb-HCV structures to complexes with truncated E2 cores. Here we describe crystal structures of full-length E2 ectodomain complexes with HEPC3 and HEPC74, revealing lock-and-key antibody-antigen interactions, E2 regions (including a target of immunogen design) that were truncated or disordered in E2 cores, and an antibody CDRH3 disulfide motif that exhibits common interactions with a conserved epitope despite different bNAb-E2 binding orientations...
November 14, 2018: Cell Host & Microbe
Sonia Maciejewski, Theodore C Pierson
The introduction of Zika virus (ZIKV) into the Americas sparked interest in the influence of heterologous antibodies on sequential ZIKV and dengue virus (DENV) infections. In this issue of Cell Host & Microbe, Fowler et al. (2018) demonstrate in mice that maternally acquired anti-ZIKV antibodies exacerbate disease following DENV challenge.
November 14, 2018: Cell Host & Microbe
Ype P de Jong
Many hurdles have plagued the development of an effective vaccine for hepatitis C virus. In this issue of Cell Host & Microbe, Kinchen et al. (2018) and Flyak et al. (2018) report on the characterization of neutralizing antibodies from individuals that spontaneously cleared infection, providing insights that promise to propel vaccine design forward.
November 14, 2018: Cell Host & Microbe
John S L Parker
In this issue of Cell Host & Microbe, Bouziat et al. (2018) and Van Winkle et al. (2018) find that the capsid gene of murine norovirus (MNV) functions as a trigger of host inflammation. These studies specifically describe how MNV-induced inflammation promotes loss of oral tolerance and persistent viral infection, respectively.
November 14, 2018: Cell Host & Microbe
Syed Saad Hussain, David F Kashatus
Mitochondrial reactive oxygen species are important anti-microbial weapons utilized by phagocytes of the innate immune system. In this issue of Cell Host and Microbe, Abuaita et al. (2018) show that in macrophages, mitochondrial-derived vesicles deliver the superoxide dismutase Sod2 to bacteria-containing phagosomes to produce hydrogen peroxide and kill invading bacteria.
November 14, 2018: Cell Host & Microbe
Meghan A Koch
Though critical for preventing fatal sepsis, the mechanisms mediating the capture of bloodstream bacteria are incompletely understood. New work by Zeng et al. (2018) demonstrates that estrogen-regulated innate antibodies protect females and newborns from death following bloodstream infection with enteropathogenic Eschericia coli.
November 14, 2018: Cell Host & Microbe
Scott H Saunders, Dianne K Newman
Extracellular electron transfer (EET) allows microbes to drive their metabolism through interactions with minerals or electrodes. In recent work, Light et al. (2018) discover a specialized EET pathway in Listeria monocytogenes with homologs in pathogens and gut commensals, suggesting that EET plays important roles in diverse environments.
November 14, 2018: Cell Host & Microbe
Romain Bouziat, Scott B Biering, Elaine Kouame, Kishan A Sangani, Soowon Kang, Jordan D Ernest, Mukund Varma, Judy J Brown, Kelly Urbanek, Terence S Dermody, Aylwin Ng, Reinhard Hinterleitner, Seungmin Hwang, Bana Jabri
Intestinal reovirus infection can trigger T helper 1 (TH 1) immunity to dietary antigen, raising the question of whether other viruses can have a similar impact. Here we show that the acute CW3 strain of murine norovirus, but not the persistent CR6 strain, induces TH 1 immunity to dietary antigen. This property of CW3 is dependent on its major capsid protein, a virulence determinant. Transcriptional profiling of mesenteric lymph nodes following infection reveals an immunopathological signature that does not segregate with protective immunity but with loss of oral tolerance, in which interferon regulatory factor 1 is critical...
November 14, 2018: Cell Host & Microbe
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