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Cell Host & Microbe

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https://www.readbyqxmd.com/read/28669672/cutaneous-leishmaniasis-induces-a-transmissible-dysbiotic-skin-microbiota-that-promotes-skin-inflammation
#1
Ciara Gimblet, Jacquelyn S Meisel, Michael A Loesche, Stephen D Cole, Joseph Horwinski, Fernanda O Novais, Ana M Misic, Charles W Bradley, Daniel P Beiting, Shelley C Rankin, Lucas P Carvalho, Edgar M Carvalho, Phillip Scott, Elizabeth A Grice
Skin microbiota can impact allergic and autoimmune responses, wound healing, and anti-microbial defense. We investigated the role of skin microbiota in cutaneous leishmaniasis and found that human patients infected with Leishmania braziliensis develop dysbiotic skin microbiota, characterized by increases in the abundance of Staphylococcus and/or Streptococcus. Mice infected with L. major exhibit similar changes depending upon disease severity. Importantly, this dysbiosis is not limited to the lesion site, but is transmissible to normal skin distant from the infection site and to skin from co-housed naive mice...
June 22, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704658/fusion-stage-of-hiv-1-entry-depends-on-virus-induced-cell-surface-exposure-of-phosphatidylserine
#2
Elena Zaitseva, Eugene Zaitsev, Kamran Melikov, Anush Arakelyan, Mariana Marin, Rafael Villasmil, Leonid B Margolis, Gregory B Melikyan, Leonid V Chernomordik
HIV-1 entry into host cells starts with interactions between the viral envelope glycoprotein (Env) and cellular CD4 receptors and coreceptors. Previous work has suggested that efficient HIV entry also depends on intracellular signaling, but this remains controversial. Here we report that formation of the pre-fusion Env-CD4-coreceptor complexes triggers non-apoptotic cell surface exposure of the membrane lipid phosphatidylserine (PS). HIV-1-induced PS redistribution depends on Ca(2+) signaling triggered by Env-coreceptor interactions and involves the lipid scramblase TMEM16F...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704657/dual-blades-the-role-of-musashi-1-in-zika-replication-and-microcephaly
#3
Robyn S Klein
Infection with Zika virus (ZIKV) during pregnancy may cause severe developmental defects in the human brain via unknown mechanisms. In a recent issue of Science, Chavali et al. (2017) identified a neural progenitor cell (NPC)-specific RNA binding protein that may underlie the high levels of ZIKV replication and apoptosis observed in these cells during congenital infections.
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704656/induction-of-inkit-by-viral-infection-negatively-regulates-antiviral-responses-through-inhibiting-phosphorylation-of-p65-and-irf3
#4
Bin Lu, Yujie Ren, Xueqin Sun, Cuijuan Han, Hongyan Wang, Yuxuan Chen, Qianqian Peng, Yongbo Cheng, Xiaoliang Cheng, Qiyun Zhu, Wenxin Li, Hong-Liang Li, Hai-Ning Du, Bo Zhong, Zan Huang
The transcription factors p65 and IRF3 play key roles in the induction of cellular antiviral responses. Phosphorylation of p65 and IRF3 is required for their activity and constitutes a key checkpoint. Here we report that viral infection induced upregulation of INKIT, an inhibitor for NF-κB and IRF3 that restricted innate antiviral responses by blocking phosphorylation of p65 and IRF3. INKIT overexpression inhibited virus-induced phosphorylation of p65 and IRF3 and expression of downstream genes. In contrast, knockdown or knockout of INKIT had the opposite effect: Inkit(-/-) mice produced elevated levels of type I interferons and proinflammatory cytokines and were more resistant to lethal viral infection compared to wild-type...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704655/war-on-viruses-lc3-recruits-gtpases
#5
Teneema Kuriakose, Thirumala-Devi Kanneganti
Interferon effector functions and autophagy are evolutionarily conserved arms of cell-autonomous immunity that restrict replication of intracellular pathogens. In this issue of Cell Host and Microbe, Biering et al., (2017) demonstrate how host cells co-opt sequential action of autophagy proteins and IFN-inducible GTPases to inhibit replication of positive-sense RNA viruses.
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704654/persistent-kshv-infection-increases-ebv-associated-tumor-formation-in%C3%A2-vivo-via-enhanced-ebv-lytic-gene-expression
#6
Donal McHugh, Nicole Caduff, Mario Henrique M Barros, Patrick C Rämer, Ana Raykova, Anita Murer, Vanessa Landtwing, Isaak Quast, Christine T Styles, Michael Spohn, Adeola Fowotade, Henri-Jacques Delecluse, Alexandra Papoudou-Bai, Yong-Moon Lee, Jin-Man Kim, Jaap Middeldorp, Thomas F Schulz, Ethel Cesarman, Andrea Zbinden, Riccarda Capaul, Robert E White, Martin J Allday, Gerald Niedobitek, David J Blackbourn, Adam Grundhoff, Christian Münz
The human tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) establish persistent infections in B cells. KSHV is linked to primary effusion lymphoma (PEL), and 90% of PELs also contain EBV. Studies on persistent KSHV infection in vivo and the role of EBV co-infection in PEL development have been hampered by the absence of small animal models. We developed mice reconstituted with human immune system components as a model for KSHV infection and find that EBV/KSHV dual infection enhanced KSHV persistence and tumorigenesis...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704653/double-the-trouble-when-herpesviruses-join-hands
#7
Un Yung Choi, Angela Park, Jae U Jung
KSHV is the etiologic agent of PEL-an aggressive lymphoma. Interestingly, EBV concurrently exists in nearly 70% of PEL cases. In this issue of Cell Host & Microbe, McHugh et al. (2017) develop humanized mouse models for EBV/KSHV co-infection and identify their complementary effect on in vivo tumor formation.
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704652/environmental-stress-causes-lethal-neuro-trauma-during-asymptomatic-viral-infections
#8
Jonathan Chow, Zsuzsa Márka, Imre Bartos, Szabolcs Márka, Jonathan C Kagan
Asymptomatic infections often proceed undetected, yet can still prime the host to be sensitive to secondary environmental stress. While the mechanisms underlying disease caused by asymptomatic infections are unknown, it is believed that productive pathogen replication is required. We report that the environmental stress of carbon dioxide (CO2) anesthesia converts an asymptomatic rhabdovirus infection in Drosophila to one that is lethal. This lethality results from a pool of infectious virus in glial cells and is regulated by the antiviral RNAi pathway of the host...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704651/synergy-between-the-host-immune-system-and-bacteriophage-is-essential-for-successful-phage-therapy-against-an-acute-respiratory-pathogen
#9
Dwayne R Roach, Chung Yin Leung, Marine Henry, Eric Morello, Devika Singh, James P Di Santo, Joshua S Weitz, Laurent Debarbieux
The rise of multi-drug-resistant (MDR) bacteria has spurred renewed interest in the use of bacteriophages in therapy. However, mechanisms contributing to phage-mediated bacterial clearance in an animal host remain unclear. We investigated the effects of host immunity on the efficacy of phage therapy for acute pneumonia caused by MDR Pseudomonas aeruginosa in a mouse model. Comparing efficacies of phage-curative and prophylactic treatments in healthy immunocompetent, MyD88-deficient, lymphocyte-deficient, and neutrophil-depleted murine hosts revealed that neutrophil-phage synergy is essential for the resolution of pneumonia...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704650/bacteria-tell-us-how-to-protect-our-intestine
#10
George Birchenough, Gunnar C Hansson
The inner colon mucus layer capacity to separate bacteria from the epithelium is dependent on bacterial colonizers signaling to the host epithelium. In this issue of Cell Host & Microbe, Wlodarska et al. (2017) demonstrate that the mucin-utilizing Peptostreptococcus russellii protects the host from inflammatory disease via metabolite signals.
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704649/indoleacrylic-acid-produced-by-commensal-peptostreptococcus-species-suppresses-inflammation
#11
Marta Wlodarska, Chengwei Luo, Raivo Kolde, Eva d'Hennezel, John W Annand, Cortney E Heim, Philipp Krastel, Esther K Schmitt, Abdifatah S Omar, Elizabeth A Creasey, Ashley L Garner, Sina Mohammadi, Daniel J O'Connell, Sahar Abubucker, Timothy D Arthur, Eric A Franzosa, Curtis Huttenhower, Leon O Murphy, Henry J Haiser, Hera Vlamakis, Jeffrey A Porter, Ramnik J Xavier
Host factors in the intestine help select for bacteria that promote health. Certain commensals can utilize mucins as an energy source, thus promoting their colonization. However, health conditions such as inflammatory bowel disease (IBD) are associated with a reduced mucus layer, potentially leading to dysbiosis associated with this disease. We characterize the capability of commensal species to cleave and transport mucin-associated monosaccharides and identify several Clostridiales members that utilize intestinal mucins...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704648/diabetes-enhances-il-17-expression-and-alters-the-oral-microbiome-to-increase-its-pathogenicity
#12
E Xiao, Marcelo Mattos, Gustavo Henrique Apolinário Vieira, Shanshan Chen, Jôice Dias Corrêa, Yingying Wu, Mayra Laino Albiero, Kyle Bittinger, Dana T Graves
Diabetes is a risk factor for periodontitis, an inflammatory bone disorder and the greatest cause of tooth loss in adults. Diabetes has a significant impact on the gut microbiota; however, studies in the oral cavity have been inconclusive. By 16S rRNA sequencing, we show here that diabetes causes a shift in oral bacterial composition and, by transfer to germ-free mice, that the oral microbiota of diabetic mice is more pathogenic. Furthermore, treatment with IL-17 antibody decreases the pathogenicity of the oral microbiota in diabetic mice; when transferred to recipient germ-free mice, oral microbiota from IL-17-treated donors induced reduced neutrophil recruitment, reduced IL-6 and RANKL, and less bone resorption...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704647/hiv-1-mediated-downmodulation-of-hla-c-impacts-target-cell-recognition-and-antiviral-activity-of-nk-cells
#13
Christian Körner, Camille R Simoneau, Philipp Schommers, Mitchell Granoff, Maja Ziegler, Angelique Hölzemer, Sebastian Lunemann, Janet Chukwukelu, Björn Corleis, Vivek Naranbhai, Douglas S Kwon, Eileen P Scully, Stephanie Jost, Frank Kirchhoff, Mary Carrington, Marcus Altfeld
It was widely accepted that HIV-1 downregulates HLA-A/B to avoid CTL recognition while leaving HLA-C unaltered in order to prevent NK cell activation by engaging inhibitory NK cell receptors, but it was recently observed that most primary isolates of HIV-1 can mediate HLA-C downmodulation. Now we report that HIV-1-mediated downmodulation of HLA-C was associated with reduced binding to its respective inhibitory receptors. Despite this, HLA-C-licensed NK cells displayed reduced antiviral activity compared to their unlicensed counterparts, potentially due to residual binding to the respective inhibitory receptors...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704646/skin-dysbiosis-goes-off-leish
#14
Tiffany C Scharschmidt
There is increasing interest in the contribution of microbes to skin disease. In this issue of Cell Host & Microbe, Gimblet et al. (2017) demonstrate that cutaneous leishmaniasis alters the human skin microbiota. In mice, this dysbiosis is transferable to naive animals, where it augments skin inflammation and disease severity.
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28669671/viral-replication-complexes-are-targeted-by-lc3-guided-interferon-inducible-gtpases
#15
Scott B Biering, Jayoung Choi, Rachel A Halstrom, Hailey M Brown, Wandy L Beatty, Sanghyun Lee, Broc T McCune, Erin Dominici, Lelia E Williams, Robert C Orchard, Craig B Wilen, Masahiro Yamamoto, Jörn Coers, Gregory A Taylor, Seungmin Hwang
All viruses with positive-sense RNA genomes replicate on membranous structures in the cytoplasm called replication complexes (RCs). RCs provide an advantageous microenvironment for viral replication, but it is unknown how the host immune system counteracts these structures. Here we show that interferon-gamma (IFNG) disrupts the RC of murine norovirus (MNV) via evolutionarily conserved autophagy proteins and the induction of IFN-inducible GTPases, which are known to destroy the membrane of vacuoles containing bacteria, protists, or fungi...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618273/sting-requires-the-adaptor-trif-to-trigger-innate-immune-responses-to-microbial-infection
#16
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
#17
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
#18
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
#19
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
#20
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
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