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https://www.readbyqxmd.com/read/29345343/mycobacterium-tuberculosis-rewiring-host-cell-signaling-to-promote-infection
#1
REVIEW
Michael D Stutz, Michelle P Clark, Marcel Doerflinger, Marc Pellegrini
The ability of Mycobacterium tuberculosis to cause disease hinges upon successfully thwarting the innate defenses of the macrophage host cell. The pathogen's trump card is its armory of virulence factors that throw normal host cell signaling into disarray. This process of subverting the macrophage begins upon entry into the cell, when M. tuberculosis actively inhibits the fusion of the bacilli-laden phagosomes with lysosomes. The pathogen then modulates an array of host signal transduction pathways, which dampens the macrophage's host-protective cytokine response, while simultaneously adapting host cell metabolism to stimulate lipid body accumulation...
December 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29343644/identification-of-genes-required-for-mycobacterium-abscessus-growth-in-vivo-with-a-prominent-role-of-the-esx-4-locus
#2
Laura Laencina, Violaine Dubois, Vincent Le Moigne, Albertus Viljoen, Laleh Majlessi, Justin Pritchard, Audrey Bernut, Laura Piel, Anne-Laure Roux, Jean-Louis Gaillard, Bérengère Lombard, Damarys Loew, Eric J Rubin, Roland Brosch, Laurent Kremer, Jean-Louis Herrmann, Fabienne Girard-Misguich
Mycobacterium abscessus, a rapidly growing mycobacterium (RGM) and an opportunistic human pathogen, is responsible for a wide spectrum of clinical manifestations ranging from pulmonary to skin and soft tissue infections. This intracellular organism can resist the bactericidal defense mechanisms of amoebae and macrophages, an ability that has not been observed in other RGM. M. abscessus can up-regulate several virulence factors during transient infection of amoebae, thereby becoming more virulent in subsequent respiratory infections in mice...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29342911/effects-of-acanthopanax-senticosus-on-brain-injury-induced-by-simulated-spatial-radiation-in-mouse-model-based-on-pharmacokinetics-and-comparative-proteomics
#3
Yingyu Zhou, Cuilin Cheng, Denis Baranenko, Jiaping Wang, Yongzhi Li, Weihong Lu
The active compounds in Acanthopanax senticosus (AS) have different pharmacokinetic characteristics in mouse models. Cmax and AUC of Acanthopanax senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, due to the pathological state of ischemia and hypoxia, which are caused by radiation. In contrast, the ability of various metabolizing enzymes to inactivate, capacity of biofilm transport decrease, and lessening of renal blood flow accounts for radiation, resulting in the accumulation of syringin and eleutheroside E in the irradiated mouse...
January 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29340604/transient-recruitment-of-m-ras-gtpase-to-phagocytic-cups-in-raw264-macrophages-during-fc%C3%AE-r-mediated-phagocytosis
#4
Youhei Egami, Nobukazu Araki
M-Ras, a member of the Ras superfamily, is known to be involved in diverse cellular processes. However, its involvement in FcγR-mediated phagocytosis remains unknown. We examined the spatiotemporal localization of M-Ras during the engulfment of IgG-opsonized erythrocytes (IgG-Es) in RAW264 macrophages. By the live-cell imaging of fluorescent protein-fused M-Ras, we found that M-Ras was localized to the membrane of phagocytic cups during the early stage of phagosome formation. Notably, ratiometric image analysis revealed that M-Ras was concentrated in the membrane of forming phagosomes...
January 11, 2018: Microscopy
https://www.readbyqxmd.com/read/29334241/transcriptional-regulation-on-the-gene-expression-signature-in-combined-allergic-rhinitis-and-asthma-syndrome
#5
Zhengdao Mao, Yujia Shi, Qi Cao, Yi Chen, Yun Sun, Zhiguang Liu, Qian Zhang, Mao Huang
AIM: This study was intended to evaluate transcriptional regulation of gene expression signatures in combined allergic rhinitis and asthma syndrome (CARAS). MATERIALS & METHODS: The blood samples of three patients with CARAS, three patients with allergic rhinitis and three normal controls were obtained. The cuffdiff, miRDeep2 and DEGseq were used to quantify the expression of genes and miRNAs, respectively. And p-value < 0.01 and false discovery rate < 0...
January 15, 2018: Epigenomics
https://www.readbyqxmd.com/read/29325545/phthiocerol-dimycocerosates-promote-access-to-the-cytosol-and-intracellular-burden-of-mycobacterium-tuberculosis-in-lymphatic-endothelial-cells
#6
Thomas R Lerner, Christophe J Queval, Antony Fearns, Urska Repnik, Gareth Griffiths, Maximiliano G Gutierrez
BACKGROUND: Phthiocerol dimycocerosates (PDIM), glycolipids found on the outer surface of virulent members of the Mycobacterium tuberculosis (Mtb) complex, are a major contributing factor to the pathogenesis of Mtb. Myelocytic cells, such as macrophages and dendritic cells, are the primary hosts for Mtb after infection and previous studies have shown multiple roles for PDIM in supporting Mtb in these cells. However, Mtb can infect other cell types. We previously showed that Mtb efficiently replicates in human lymphatic endothelial cells (hLECs) and that the hLEC cytosol acts as a reservoir for Mtb in humans...
January 4, 2018: BMC Biology
https://www.readbyqxmd.com/read/29322608/comparison-of-listeriolysin-o-and-phospholipases-plca-and-plcb-activities-and-initial-intracellular-growth-capability-among-food-and-clinical-strains-of-listeria-monocytogenes
#7
M Kanki, H Naruse, K Kawatsu
AIMS: We investigated whether Listeria monocytogenes strains differ in their ability to escape from the primary phagosome after internalization into human intestinal epithelial cells. METHODS AND RESULTS: Food and clinical strains were used to study specific alleles; the activities of listeriolysin O (LLO) and phospholipases PlcA and PlcB, which promote rupture of the phagocytic vacuole; and initial intracellular bacterial growth in Caco-2 cells. Results showed no difference in LLO activities between food and clinical strains or among serotypes...
January 11, 2018: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/29321691/deciphering-the-nature-of-the-coral-chromera-association
#8
Amin R Mohamed, Vivian R Cumbo, Saki Harii, Chuya Shinzato, Cheong Xin Chan, Mark A Ragan, Nori Satoh, Eldon E Ball, David J Miller
Since the discovery of Chromera velia as a novel coral-associated microalga, this organism has attracted interest because of its unique evolutionary position between the photosynthetic dinoflagellates and the parasitic apicomplexans. The nature of the relationship between Chromera and its coral host is controversial. Is it a mutualism, from which both participants benefit, a parasitic relationship, or a chance association? To better understand the interaction, larvae of the common Indo-Pacific reef-building coral Acropora digitifera were experimentally infected with Chromera, and the impact on the host transcriptome was assessed at 4, 12, and 48 h post-infection using Illumina RNA-Seq technology...
January 10, 2018: ISME Journal
https://www.readbyqxmd.com/read/29317718/protein-tyrosine-kinase-ptka-is-required-for-mycobacterium-tuberculosis-growth-in-macrophages
#9
Dennis Wong, Wu Li, Joseph D Chao, Peifu Zhou, Gagandeep Narula, Clement Tsui, Mary Ko, Jianping Xie, Carlos Martinez-Frailes, Yossef Av-Gay
Protein phosphorylation plays a key role in Mycobacterium tuberculosis (Mtb) physiology and pathogenesis. We have previously shown that a secreted protein tyrosine phosphatase, PtpA, is essential for Mtb inhibition of host macrophage acidification and maturation, and is a substrate of the protein tyrosine kinase, PtkA, encoded in the same operon. In this study, we constructed a ∆ptkA deletion mutant in Mtb and found that the mutant exhibited impaired intracellular survival in the THP-1 macrophage infection model, correlated with the strain's inability to inhibit macrophage phagosome acidification...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29315318/correlative-light-and-immuno-electron-microscopy-of-retinal-tissue-cryostat-sections
#10
Thomas Burgoyne, Amelia Lane, William E Laughlin, Michael E Cheetham, Clare E Futter
Correlative light-electron microscopy (CLEM) is a powerful technique allowing localisation of specific macromolecules within fluorescence microscopy (FM) images to be mapped onto corresponding high-resolution electron microscopy (EM) images. Existing methods are applicable to limited sample types and are technically challenging. Here we describe novel methods to perform CLEM and immuno-electron microscopy (iEM) on cryostat sections utilising the popular FM embedding solution, optimal cutting temperature (OCT) compound...
2018: PloS One
https://www.readbyqxmd.com/read/29313424/why-macrophages-cannot-lap-up-tb
#11
Stefan Köster, Sandeep Upadhyay, Jennifer A Philips
M. tuberculosis causes an enormous worldwide burden of disease. Its success depends upon subverting the antimicrobial capacity of macrophages. We have known for decades that M. tuberculosis impairs phagosomal trafficking to avoid lysosomal degradation, but the mechanism is unclear. Recent work has described a phagolysosomal pathway called LC3-associated phagocytosis (LAP), in which LC3 associates with microbe-containing phagosomes. Macrophage pathogen recognition receptors (PRRs) initiate LAP, and NADPH oxidase and RUBCN/RUBICON are required for LAP...
January 9, 2018: Autophagy
https://www.readbyqxmd.com/read/29310530/unc569-induced-morphological-changes-in-pigment-epithelia-and-photoreceptor-cells-in-the-retina-through-mertk-inhibition-in-mice
#12
Ayako Sayama, Keiko Okado, Koichi Nakamura, Tatsuya Kawaguchi, Takuma Iguchi, Toshihiko Makino, Koichi Yabe, Kiyonori Kai, Kazuhiko Mori
Mer proto-oncogene tyrosine kinase (MerTK), which is expressed in the retinal pigment epithelium (RPE), regulates phagocytosis of shed photoreceptor outer segments (POS). To investigate the effects of drug-induced MerTK inhibition on the retina, UNC569, a specific MerTK inhibitor, was orally administered to male mice at a concentration of 60, 100, or 150 mg/kg for up to 14 days. Furthermore, MerTK inhibition in the retinal tissue sample was examined using a phosphorylation assay following a single dose of UNC569 at 100 mg/kg...
January 1, 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29305332/morphological-and-functional-characterization-of-hemocytes-from-two-deep-sea-vesicomyid-clams-phreagena-okutanii-and-abyssogena-phaseoliformis
#13
Akihiro Tame, Genki Ozawa, Tadashi Maruyama, Takao Yoshida
Deep-sea vesicomyid clams harboring intracellular symbiotic sulfur-oxidizing bacteria are often dominant in chemosynthetic animal communities. Although they are known to have erythrocytes, little is known about other hemocytes. To investigate the types and roles of various hemocytes in vesicomyid clams, we performed morphological, histochemical and functional characterization of the hemocytes in two species, Phreagena okutanii, collected from 873 to 978 m depth, and Abyssogena phaseoliformis, from 5199 to 5355 m...
January 2, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29301939/interleukin-10-suppresses-lysosome-mediated-killing-of-brucella-abortus-in-cultured-macrophages
#14
Huynh Tan Hop, Alisha Wehdnesday Bernardo Reyes, Tran Xuan Ngoc Huy, Lauren Togonon Arayan, WonGi Min, Hu Jang Lee, Man Hee Rhee, Hong Hee Chang, Suk Kim
Brucella abortus is a Gram-negative zoonotic pathogen for which there is no 100% effective vaccine. Phagosomes in B. abortus-infected cells fail to mature allowing the pathogen to survive and proliferate. Interleukin 10 (IL-10) promotes B. abortus persistence in macrophages by mechanisms that are not fully understood. In this study, we investigated the regulatory role of IL-10 in the immune response to B. abortus infection. B. abortus-infected macrophages were treated with either IL10 siRNA or recombinant IL-10 (rIL-10) and the expression of phagolysosome- or inflammation-related genes was evaluated by qRT-PCR and Western blot...
January 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29287983/inducible-nitric-oxide-synthase-in-innate-immune-cells-is-important-for-restricting-cyst-formation-of-toxoplasma-gondii-in-the-brain-but-not-required-for-the-protective-immune-process-to-remove-the-cysts
#15
Qila Sa, Ashish Tiwari, Eri Ochiai, Jeremi Mullins, Yasuhiro Suzuki
Significantly larger numbers of Toxoplasma gondii cysts were detected in the brains of RAG1-/-NOS2-/- than RAG1-/- mice following infection. In contrast, the cyst numbers markedly decreased in a same manner in both strains of mice after receiving CD8+ immune T cells. Thus, NOS2-mediated innate immunity is important for inhibiting formation of cysts in the brain but not required for the T cell-initiated cyst removal, which is associated with phagocyte accumulation. Treatment with chloroquine, an inhibitor of endolysosomal acidification, partially but significantly inhibited the T cell-mediated cyst removal, suggesting that phagosome-lysomose fusion could be involved in the T...
December 26, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/29282279/renitence-vacuoles-facilitate-protection-against-phagolysosomal-damage-in-activated-macrophages
#16
Amanda O Wong, Matangi Marthi, Zachary I Mendel, Brian Gregorka, Michele S Swanson, Joel A Swanson
As professional phagocytes, macrophages are susceptible to endolysosomal membrane damage inflicted by the pathogens and noxious particles they ingest. Whether macrophages have mechanisms for limiting such damage is not well understood. Previously we reported a phenomenon, termed "inducible renitence," in which LPS activation of macrophages protected their endolysosomes against damage initiated by the phagocytosis of silica beads. To gain mechanistic insight into the process, we analyzed the kinetics of renitence and morphological features of LPS-activated versus resting macrophages following silica bead-mediated injury...
December 27, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29281743/hdac6-controls-innate-immune-and-autophagy-responses-to-tlr-mediated-signalling-by-the-intracellular-bacteria-listeria-monocytogenes
#17
Olga Moreno-Gonzalo, Marta Ramírez-Huesca, Noelia Blas-Rus, Danay Cibrián, María Laura Saíz, Inmaculada Jorge, Emilio Camafeita, Jesús Vázquez, Francisco Sánchez-Madrid
Recent evidence on HDAC6 function underlines its role as a key protein in the innate immune response to viral infection. However, whether HDAC6 regulates innate immunity during bacterial infection remains unexplored. To assess the role of HDAC6 in the regulation of defence mechanisms against intracellular bacteria, we used the Listeria monocytogenes (Lm) infection model. Our data show that Hdac6-/- bone marrow-derived dendritic cells (BMDCs) have a higher bacterial load than Hdac6+/+ cells, correlating with weaker induction of IFN-related genes, pro-inflammatory cytokines and nitrite production after bacterial infection...
December 27, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29279409/listeria-monocytogenes-triggers-noncanonical-autophagy-upon-phagocytosis-but-avoids-subsequent-growth-restricting-xenophagy
#18
Gabriel Mitchell, Mandy I Cheng, Chen Chen, Brittney N Nguyen, Aaron T Whiteley, Sara Kianian, Jeffery S Cox, Douglas R Green, Kent L McDonald, Daniel A Portnoy
Xenophagy is a selective macroautophagic process that protects the host cytosol by entrapping and delivering microbes to a degradative compartment. Both noncanonical autophagic pathways and xenophagy are activated by microbes during infection, but the relative importance and function of these distinct processes are not clear. In this study, we used bacterial and host mutants to dissect the contribution of autophagic processes responsible for bacterial growth restriction of Listeria monocytogenesL. monocytogenes is a facultative intracellular pathogen that escapes from phagosomes, grows in the host cytosol, and avoids autophagy by expressing three determinants of pathogenesis: two secreted phospholipases C (PLCs; PlcA and PlcB) and a surface protein (ActA)...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29259085/a-specialized-peptidoglycan-synthase-promotes-salmonella-cell-division-inside-host-cells
#19
Sónia Castanheira, Juan J Cestero, Gadea Rico-Pérez, Pablo García, Felipe Cava, Juan A Ayala, M Graciela Pucciarelli, Francisco García-Del Portillo
Bacterial cell division has been studied extensively under laboratory conditions. Despite being a key event in the bacterial cell cycle, cell division has not been explored in vivo in bacterial pathogens interacting with their hosts. We discovered in Salmonella enterica serovar Typhimurium a gene absent in nonpathogenic bacteria and encoding a peptidoglycan synthase with 63% identity to penicillin-binding protein 3 (PBP3). PBP3 is an essential cell division-specific peptidoglycan synthase that builds the septum required to separate daughter cells...
December 19, 2017: MBio
https://www.readbyqxmd.com/read/29248928/differential-kinetics-of-aspergillus-nidulans-and-aspergillus-fumigatus-phagocytosis
#20
Mark S Gresnigt, Katharina L Becker, Floris Leenders, M Fernanda Alonso, Xiaowen Wang, Jacques F Meis, Judith M Bain, Lars P Erwig, Frank L van de Veerdonk
Invasive aspergillosis mainly occurs in immunocompromised patients and is commonly caused by Aspergillus fumigatus, while A.nidulans is rarely the causative agent. However, in chronic granulomatous disease (CGD) patients, A. nidulans is a frequent cause of invasive aspergillosis and is associated with higher mortality. Immune recognition of A. nidulans was compared to A. fumigatus to offer an insight into why A. nidulans infections are prevalent in CGD. Live cell imaging with J774A.1 macrophage-like cells and LC3-GFP-mCherry bone marrow-derived macrophages (BMDMs) revealed that phagocytosis of A...
December 16, 2017: Journal of Innate Immunity
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