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Cell Host & Microbe

Rishi Drolia, Shivendra Tenguria, Abigail C Durkes, Jerrold R Turner, Arun K Bhunia
Intestinal epithelial cells are the first line of defense against enteric pathogens, yet bacterial pathogens, such as Listeria monocytogenes, can breach this barrier. We show that Listeria adhesion protein (LAP) induces intestinal epithelial barrier dysfunction to promote bacterial translocation. These disruptions are attributed to the production of pro-inflammatory cytokines TNF-α and IL-6, which is observed in mice challenged with WT and isogenic strains lacking the surface invasion protein Internalin A (ΔinlA), but not a lap- mutant...
March 28, 2018: Cell Host & Microbe
Jagadish Beloor, Nyree Maes, Irfan Ullah, Pradeep Uchil, Andrew Jackson, Erol Fikrig, Sang Kyung Lee, Priti Kumar
No vaccines or therapeutics are licensed for West Nile virus (WNV), a mosquito-transmitted neuroencephalitic flavivirus. The small interfering RNA siFvEJW targets a conserved sequence within the WNV E protein and limits virus infection. Using a rabies virus-derived neuron-targeting peptide (RVG9R) and an intranasal route for delivering siFvEJW to the CNS, we demonstrate that treatment of WNV-infected mice at late stages of neuroinvasive disease results in recovery. Selectively targeting virus in the CNS lowers viral burdens in the brain, reduces neuropathology, and results in a 90% survival rate at 5-6 days post-infection (when viral titers peak in the CNS), while placebo-treated mice succumb by days 9-10...
March 21, 2018: Cell Host & Microbe
Nydiaris Hernández-Santos, Darin L Wiesner, J Scott Fites, Andrew J McDermott, Thomas Warner, Marcel Wüthrich, Bruce S Klein
Lung epithelial cells (LECs) are strategically positioned in the airway mucosa to provide barrier defense. LECs also express pattern recognition receptors and a myriad of immune genes, but their role in immunity is often concealed by the activities of "professional" immune cells, particularly in the context of fungal infection. Here, we demonstrate that NF-κB signaling in LECs is essential for immunity against the pulmonary fungal pathogen Blastomyces dermatitidis. LECs orchestrate innate antifungal immunity by augmenting the numbers of interleukin-17A (IL-17A)- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing innate lymphocytes, specifically "natural" Th17 (nTh17) cells...
March 20, 2018: Cell Host & Microbe
Jiangbo Fan, Pengfei Bai, Yuese Ning, Jiyang Wang, Xuetao Shi, Yehui Xiong, Kai Zhang, Feng He, Chongyang Zhang, Ruyi Wang, Xiangzong Meng, Jinggeng Zhou, Mo Wang, Gautam Shirsekar, Chan Ho Park, Maria Bellizzi, Wende Liu, Jong-Seong Jeon, Ye Xia, Libo Shan, Guo-Liang Wang
Programmed cell death (PCD) plays critical roles in plant immunity but must be regulated to prevent excessive damage. The E3 ubiquitin ligase SPL11 negatively regulates PCD and immunity in plants. We show that SPL11 cell-death suppressor 2 (SDS2), an S-domain receptor-like kinase, positively regulates PCD and immunity in rice by engaging and regulating SPL11 and related kinases controlling defense responses. An sds2 mutant shows reduced immune responses and enhanced susceptibility to the blast fungus Magnaporthe oryzae...
March 20, 2018: Cell Host & Microbe
Anna Staffas, Marina Burgos da Silva, Ann E Slingerland, Amina Lazrak, Curtis J Bare, Corey D Holman, Melissa D Docampo, Yusuke Shono, Benjamin Durham, Amanda J Pickard, Justin R Cross, Christoph Stein-Thoeringer, Enrico Velardi, Jennifer J Tsai, Lorenz Jahn, Hillary Jay, Sophie Lieberman, Odette M Smith, Eric G Pamer, Jonathan U Peled, David E Cohen, Robert R Jenq, Marcel R M van den Brink
Bone marrow transplantation (BMT) offers curative potential for patients with high-risk hematologic malignancies, but the post-transplantation period is characterized by profound immunodeficiency. Recent studies indicate that the intestinal microbiota not only regulates mucosal immunity, but can also contribute to systemic immunity and hematopoiesis. Using antibiotic-mediated microbiota depletion in a syngeneic BMT mouse model, here we describe a role for the intestinal flora in hematopoietic recovery after BMT...
March 19, 2018: Cell Host & Microbe
Enzo Z Poirier, Bertsy Goic, Lorena Tomé-Poderti, Lionel Frangeul, Jérémy Boussier, Valérie Gausson, Hervé Blanc, Thomas Vallet, Hyelee Loyd, Laura I Levi, Sophie Lanciano, Chloé Baron, Sarah H Merkling, Louis Lambrechts, Marie Mirouze, Susan Carpenter, Marco Vignuzzi, Maria-Carla Saleh
The RNAi pathway confers antiviral immunity in insects. Virus-specific siRNA responses are amplified via the reverse transcription of viral RNA to viral DNA (vDNA). The nature, biogenesis, and regulation of vDNA are unclear. We find that vDNA produced during RNA virus infection of Drosophila and mosquitoes is present in both linear and circular forms. Circular vDNA (cvDNA) is sufficient to produce siRNAs that confer partially protective immunity when challenged with a cognate virus. cvDNAs bear homology to defective viral genomes (DVGs), and DVGs serve as templates for vDNA and cvDNA synthesis...
February 27, 2018: Cell Host & Microbe
Kyung-Ah Lee, Kyu-Chan Cho, Boram Kim, In-Hwan Jang, Kibum Nam, Young Eun Kwon, Myungjin Kim, Do Young Hyeon, Daehee Hwang, Jae-Hong Seol, Won-Jae Lee
DUOX, a member of the NADPH oxidase family, acts as the first line of defense against enteric pathogens by producing microbicidal reactive oxygen species. DUOX is activated upon enteric infection, but the mechanisms regulating DUOX activity remain incompletely understood. Using Drosophila genetic tools, we show that enteric infection results in "pro-catabolic" signaling that initiates metabolic reprogramming of enterocytes toward lipid catabolism, which ultimately governs DUOX homeostasis. Infection induces signaling cascades involving TRAF3 and kinases AMPK and WTS, which regulate TOR kinase to control the balance of lipogenesis versus lipolysis...
February 8, 2018: Cell Host & Microbe
Joel R Wilmore, Brian T Gaudette, Daniela Gomez Atria, Tina Hashemi, Derek D Jones, Christopher A Gardner, Stephen D Cole, Ana M Misic, Daniel P Beiting, David Allman
Serum immunoglobulin A (IgA) antibodies are readily detected in mice and people, but the mechanisms underlying the induction of serum IgA and its role in host protection remain uncertain. We report that select commensal bacteria induce several facets of systemic IgA-mediated immunity. Exposing conventional mice to a unique but natural microflora that included several members of the Proteobacteria phylum led to T cell-dependent increases in serum IgA levels and the induction of large numbers of IgA-secreting plasma cells in the bone marrow...
February 7, 2018: Cell Host & Microbe
Jiazheng Xie, Yang Li, Xurui Shen, Geraldine Goh, Yan Zhu, Jie Cui, Lin-Fa Wang, Zheng-Li Shi, Peng Zhou
Compared with terrestrial mammals, bats have a longer lifespan and greater capacity to co-exist with a variety of viruses. In addition to cytosolic DNA generated by these viral infections, the metabolic demands of flight cause DNA damage and the release of self-DNA into the cytoplasm. However, whether bats have an altered DNA sensing/defense system to balance high cytosolic DNA levels remains an open question. We demonstrate that bats have a dampened interferon response due to the replacement of the highly conserved serine residue (S358) in STING, an essential adaptor protein in multiple DNA sensing pathways...
February 6, 2018: Cell Host & Microbe
Nil Gural, Liliana Mancio-Silva, Alex B Miller, Ani Galstian, Vincent L Butty, Stuart S Levine, Rapatbhorn Patrapuvich, Salil P Desai, Sebastian A Mikolajczak, Stefan H I Kappe, Heather E Fleming, Sandra March, Jetsumon Sattabongkot, Sangeeta N Bhatia
The unique relapsing nature of Plasmodium vivax infection is a major barrier to malaria eradication. Upon infection, dormant liver-stage forms, hypnozoites, linger for weeks to months and then relapse to cause recurrent blood-stage infection. Very little is known about hypnozoite biology; definitive biomarkers are lacking and in vitro platforms that support phenotypic studies are needed. Here, we recapitulate the entire liver stage of P. vivax in vitro, using a multiwell format that incorporates micropatterned primary human hepatocyte co-cultures (MPCCs)...
February 6, 2018: Cell Host & Microbe
Bernard Charroux, Florence Capo, C Léopold Kurz, Sabine Peslier, Delphine Chaduli, Annelise Viallat-Lieutaud, Julien Royet
Gut-associated bacteria produce metabolites that both have a local influence on the intestinal tract and act at a distance on remote organs. In Drosophila, bacteria-derived peptidoglycan (PGN) displays such a dual role. PGN triggers local antimicrobial peptide production by enterocytes; it also activates systemic immune responses in fat-body cells and modulates fly behavior by acting on neurons. How these responses to a single microbiota-derived compound are simultaneously coordinated is not understood. We show here that the PGRP-LB locus generates both cytosolic and secreted PGN-cleaving enzymes...
January 30, 2018: Cell Host & Microbe
Sicai Zhang, Francois Lebreton, Michael J Mansfield, Shin-Ichiro Miyashita, Jie Zhang, Julia A Schwartzman, Liang Tao, Geoffrey Masuyer, Markel Martínez-Carranza, Pål Stenmark, Michael S Gilmore, Andrew C Doxey, Min Dong
Botulinum neurotoxins (BoNTs), produced by various Clostridium strains, are a family of potent bacterial toxins and potential bioterrorism agents. Here we report that an Enterococcus faecium strain isolated from cow feces carries a BoNT-like toxin, designated BoNT/En. It cleaves both VAMP2 and SNAP-25, proteins that mediate synaptic vesicle exocytosis in neurons, at sites distinct from known BoNT cleavage sites on these two proteins. Comparative genomic analysis determines that the E. faecium strain carrying BoNT/En is a commensal type and that the BoNT/En gene is located within a typical BoNT gene cluster on a 206 kb putatively conjugative plasmid...
January 26, 2018: Cell Host & Microbe
Jin A Cho, Ann-Hwee Lee, Barbara Platzer, Benedict C S Cross, Brooke M Gardner, Heidi De Luca, Phi Luong, Heather P Harding, Laurie H Glimcher, Peter Walter, Edda Fiebiger, David Ron, Jonathan C Kagan, Wayne I Lencer
No abstract text is available yet for this article.
April 11, 2018: Cell Host & Microbe
Netusha Thevaranjan, Alicja Puchta, Christian Schulz, Avee Naidoo, J C Szamosi, Chris P Verschoor, Dessi Loukov, Louis P Schenck, Jennifer Jury, Kevin P Foley, Jonathan D Schertzer, Maggie J Larché, Donald J Davidson, Elena F Verdú, Michael G Surette, Dawn M E Bowdish
No abstract text is available yet for this article.
April 11, 2018: Cell Host & Microbe
Caroline C Gillis, Elizabeth R Hughes, Luisella Spiga, Maria G Winter, Wenhan Zhu, Tatiane Furtado de Carvalho, Rachael B Chanin, Cassie L Behrendt, Lora V Hooper, Renato L Santos, Sebastian E Winter
No abstract text is available yet for this article.
April 11, 2018: Cell Host & Microbe
Christa Geeke Toenhake, Sabine Anne-Kristin Fraschka, Mahalingam Shanmugiah Vijayabaskar, David Robert Westhead, Simon Jan van Heeringen, Richárd Bártfai
Underlying the development of malaria parasites within erythrocytes and the resulting pathogenicity is a hardwired program that secures proper timing of gene transcription and production of functionally relevant proteins. How stage-specific gene expression is orchestrated in vivo remains unclear. Here, using the assay for transposase accessible chromatin sequencing (ATAC-seq), we identified ∼4,000 regulatory regions in P. falciparum intraerythrocytic stages. The vast majority of these sites are located within 2 kb upstream of transcribed genes and their chromatin accessibility pattern correlates positively with abundance of the respective mRNA transcript...
April 11, 2018: Cell Host & Microbe
Ashwanth C Francis, Gregory B Melikyan
The HIV-1 core consists of capsid proteins (CA) surrounding viral genomic RNA. After virus-cell fusion, the core enters the cytoplasm and the capsid shell is lost through uncoating. CA loss precedes nuclear import and HIV integration into the host genome, but the timing and location of uncoating remain unclear. By visualizing single HIV-1 infection, we find that CA is required for core docking at the nuclear envelope (NE), whereas early uncoating in the cytoplasm promotes proteasomal degradation of viral complexes...
April 11, 2018: Cell Host & Microbe
Srdjan M Dragovic, Tolulope A Agunbiade, Marianna Freudzon, Jing Yang, Andrew K Hastings, Tyler R Schleicher, Xia Zhou, Sam Craft, Yu-Min Chuang, Floricel Gonzalez, Youquan Li, Gabriela Hrebikova, Abhai Tripathi, Godfree Mlambo, Lionel Almeras, Alexander Ploss, George Dimopoulos, Erol Fikrig
Plasmodium infection begins with the bite of an anopheline mosquito, when sporozoites along with saliva are injected into a vertebrate host. The role of the host responses to mosquito saliva components in malaria remains unclear. We observed that antisera against Anopheles gambiae salivary glands partially protected mice from mosquito-borne Plasmodium infection. Specifically, antibodies to A. gambiae TRIO (AgTRIO), a mosquito salivary gland antigen, contributed to the protection. Mice administered AgTRIO antiserum showed lower Plasmodium liver burden and decreased parasitemia when exposed to infected mosquitoes...
April 11, 2018: Cell Host & Microbe
Neeraj K Lal, Ugrappa Nagalakshmi, Nicholas K Hurlburt, Rosalva Flores, Aurelie Bak, Pyae Sone, Xiyu Ma, Gaoyuan Song, Justin Walley, Libo Shan, Ping He, Clare Casteel, Andrew J Fisher, Savithramma P Dinesh-Kumar
Plants employ cell-surface pattern recognition receptors (PRRs) to detect pathogens. Although phytohormones produced during PRR signaling play an essential role in innate immunity, a direct link between PRR activation and hormone regulation is unknown. EFR is a PRR that recognizes bacterial EF-Tu and activates immune signaling. Here we report that EFR regulates the phytohormone jasmonic acid (JA) through direct phosphorylation of a receptor-like cytoplasmic kinase, BIK1. The BIK1 structure revealed that the EFR-phosphorylated sites reside on a uniquely extended loop away from the BIK1 kinase core domain...
April 11, 2018: Cell Host & Microbe
Kristina Martinez-Guryn, Nathaniel Hubert, Katya Frazier, Saskia Urlass, Mark W Musch, Patricia Ojeda, Joseph F Pierre, Jun Miyoshi, Timothy J Sontag, Candace M Cham, Catherine A Reardon, Vanessa Leone, Eugene B Chang
The gut microbiota play important roles in lipid metabolism and absorption. However, the contribution of the small bowel microbiota of mammals to these diet-microbe interactions remains unclear. We determine that germ-free (GF) mice are resistant to diet-induced obesity and malabsorb fat with specifically impaired lipid digestion and absorption within the small intestine. Small bowel microbes are essential for host adaptation to dietary lipid changes by regulating gut epithelial processes involved in their digestion and absorption...
April 11, 2018: Cell Host & Microbe
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