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Infection and Immunity

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https://www.readbyqxmd.com/read/28320838/early-immune-regulatory-changes-in-a-primary-controlled-human-plasmodium-vivax-infection-cd1c-mdc-maturation-arrest-induction-of-the-kynurenine-pathway-and-regulatory-t-cell-activation
#1
Tonia Woodberry, Jessica R Loughland, Gabriela Minigo, Julie G Burel, Fiona H Amante, Kim A Piera, Yvette McNeil, Tsin W Yeo, Michael F Good, Denise L Doolan, Christian R Engwerda, James S McCarthy, Nicholas M Anstey
Plasmodium vivax malaria remains a major public health problem. The requirements for acquisition of protective immunity to this species are not clear. Dendritic cells (DC) are essential for immune cell priming, but also perform immune-regulatory functions, along with regulatory T cells (Treg). An important function of DC involves activation of the kynurenine pathway via indoleamine 2,3-dioxygenase (IDO). Using a controlled human experimental infection study with blood-stage P. vivax, we characterised plasmacytoid DC (pDC) and myeloid DC (mDC) subset maturation, CD4(+)CD25(+)CD127(lo) Treg activation and IDO activity...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28320837/the-suf-iron-sulfur-cluster-biosynthetic-system-is-essential-in-staphylococcus-aureus-and-decreased-suf-function-results-in-global-metabolic-defects-and-reduced-survival-in-human-neutrophils
#2
Christina A Roberts, Hassan M Al-Tameemi, Ameya A Mashruwala, Zuelay Rosario-Cruz, Unnati Chauhan, William E Sause, Victor J Torres, William J Belden, Jeffrey M Boyd
Staphylococcus aureus remains a causative agent for morbidity and mortality worldwide. This is, in part, a result of antimicrobial resistance highlighting the need to uncover novel antibiotic targets and discover new therapeutic agents. In the present study we explored the possibility that iron-sulfur (Fe-S) cluster synthesis is a viable antimicrobial target. RNA interference studies established that Suf (sulfur mobilization) dependent Fe-S cluster synthesis is essential in S. aureus We found that sufCDSUB were cotranscribed and suf transcription was positively influenced by sigma factor B...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28320836/adaptive-upregulation-of-clumping-factor-a-clfa-by-s-aureus-in-the-obese-type-2-diabetic-host-mediates-increased-virulence
#3
Christopher W Farnsworth, Eric M Schott, Sarah E Jensen, Jacob Zukoski, Abigail M Benvie, Majed A Refaai, Stephen L Kates, Edward M Schwarz, Michael J Zuscik, Steven R Gill, Robert A Mooney
Obesity and associated type 2 diabetes (T2D) are important risk factors for infection following orthopaedic implant surgery. Staphylococcus aureus, the most common pathogen in bone infections, adapts to multiple environments to survive and evade host immune responses. Whether adaptation of S. aureus to the unique environment of the obese/T2D host accounts for its increased virulence and persistence in this population is unknown. Thus, we assessed implant-associated osteomyelitis in normal versus high fat-diet obese/T2D mice and found that S...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28320835/genetic-analysis-of-neisseria-meningitidis-sequence-type-7-serogroup-x-originating-from-serogroup-a
#4
Bingqing Zhu, Pingping Yao, Leyi Zhang, Yuan Gao, Li Xu, Na Xie, Zhujun Shao
Neisseria meningitidis causes meningococcal disease often resulting in fulminant meningitis, sepsis and death. Vaccination programmes have been developed to prevent infection of this pathogen but serogroup replacement is a problem. Capsular switching has been an important survival mechanism for N. meningitidis allowing the organism to evolve in the present vaccine era. However, related mechanisms have not been completely elucidated. Genetic analysis of capsular switching between diverse serogroups would help further our understanding of this pathogen...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28320834/early-intracellular-trafficking-of-granulibacter-bethesdensis-in-human-macrophages
#5
Jessica Chu, Margery G Smelkinson, David W Dorward, Kol A Zarember, John I Gallin
Granulibacter bethesdensis is a Gram-negative bacterium that infects patients with Chronic Granulomatous Disease (CGD), a primary immunodeficiency marked by a defect in NOX2, the phagocyte nicotinamide adenine dinucleotide phosphate oxidase. Previous studies have shown that NOX2 is essential for killing of G. bethesdensis by neutrophils and monocytes and that bacteriostatic activity of monocyte derived macrophages (MDM) requires NOX2 and IFNγ-pretreatment. To determine if G. bethesdensis evades phagolysosomal killing, a host defense pathway intact in both normal and CGD MDM, or occupies a distinct intracellular niche in CGD MDM, we assessed the trafficking patterns of this organism...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28289147/gfpuv-expressing-recombinant-rickettsia-typhi-a-useful-tool-for-the-study-of-pathogenesis-and-cd8-t-cell-immunology-in-rickettsia-typhi-infection
#6
Matthias Hauptmann, Nicole Burkhardt, Ulrike Munderloh, Svenja Kuehl, Ulricke Richardt, Susanne Krasemann, Kristin Hartmann, Till Krech, Bernhard Fleischer, Christian Keller, Anke Osterloh
Rickettsia (R) typhi is the causative agent of endemic typhus, a disease that occurs wordwide with increasing incidence and can be fatal. Because of its obligate intracellular life style, genetic manipulation of this pathogen is difficult. Nonetheless, in recent years genetic manipulation tools have been successfully applied to rickettsiae. We describe here for the first time the transformation of R. typhi with the pRAM18dRGA plasmid that originally derives from R. amblyommatis and encodes for the expression of GFP(uv) Transformed R...
March 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28289146/the-pseudomonas-aeruginosa-prrf-small-rnas-regulate-iron-homeostasis-during-acute-murine-lung-infection
#7
Alexandria A Reinhart, Angela T Nguyen, Luke K Brewer, Justin Bevere, Jace W Jones, Maureen A Kane, F Heath Damron, Mariette Barbier, Amanda G Oglesby-Sherrouse
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that requires iron for virulence. Iron homeostasis is maintained in part by the PrrF1 and PrrF2 small RNAs, which block the expression of iron-containing proteins in iron-depleted conditions. The PrrF sRNAs also promote the production of the Pseudomonas quinolone signal, a quorum sensing molecule that activates the expression of several virulence genes. The tandem arrangement of the prrF genes allows for expression of a third sRNA, PrrH, which is predicted to regulate gene expression through its unique sequence derived from the prrF1-prrF2 intergenic sequence (the PrrH-IG sequence)...
March 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28289145/irf6-promotes-keratinocyte-differentiation-in-response-to-porphyromonas-gingivalis
#8
Jennifer Huynh, Glen M Scholz, Jiamin Aw, Eric C Reynolds
We recently demonstrated that the expression of the Interferon regulatory factor 6 (IRF6) transcription factor in oral keratinocytes was stimulated by the periodontal pathogen Porphyromonas gingivalis Here, we have established that IRF6 promotes the differentiation of oral keratinocytes in response to P. gingivalis This was evidenced by the IRF6-dependent upregulation of specific markers of keratinocyte terminal differentiation (e.g. Involucrin, IVL; Keratin 13, KRT13), together with additional transcriptional regulators of keratinocyte differentiation, including Grainyhead-like 3 (GRHL3) and Ovo-like zinc finger 1 (OVOL1)...
March 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28289144/staphylococcus-aureus-survives-in-cystic-fibrosis-macrophages-forming-a-reservoir-for-chronic-pneumonia
#9
Cao Li, Yuqing Wu, Andrea Riehle, Jie Ma, Markus Kamler, Erich Gulbins, Heike Grassmé
Staphylococcus aureus (S. aureus) plays an important role in sepsis, pneumonia, wound infections and cystic fibrosis (CF), which is caused by mutations of the cystic fibrosis transmembrane conductance regulator (Cftr). Pulmonary S. aureus infections in CF often occur very early and prior to colonization with other pathogens, in particular Pseudomonas aeruginosa Here, we demonstrate that CF mice are highly susceptible to pulmonary infections with S. aureus and fail to clear the pathogen during infection. S. aureus is internalized by Cftr-deficient macrophages in the lung, but these macrophages are unable to kill intracellular bacteria...
March 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28264910/the-expanding-role-of-type-ii-secretion-in-bacterial-pathogenesis-and-beyond
#10
Nicholas P Cianciotto, Richard C White
Type II secretion (T2S) is one means by which Gram-negative pathogens secrete proteins into the extracellular milieu and/or host organisms. Based upon recent genome sequencing, it is clear that T2S is largely restricted to the Proteobacteria, occurring in many, but not all genera in the α-, β-, γ-, and δ- classes. Prominent human and/or animal pathogens that express a T2S system(s) include Acinetobacter baumannii, Burkholderia pseudomallei, Chlamydia trachomatis, Escherichia coli, Klebsiella pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Vibrio cholerae, and Yersinia enterocolitica T2S-expressing plant pathogens include Dickeya dadantii, Erwinia amylovora, Pectobacterium carotovorum, Ralstonia solanacearum, Xanthomonas campestris, Xanthomonas oryzae, and Xylella fastidiosa T2S also occurs in non-pathogenic bacteria, facilitating symbioses, among other things...
March 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28264909/promotion-and-rescue-of-intracellular-brucella-neotomae-replication-during-co-infection-with-legionella-pneumophila
#11
Yoon-Suk Kang, James E Kirby
We established a new Brucella neotomaein vitro model system for study of type IV secretion system-dependent (T4SS) pathogenesis in the Brucella genus. Importantly, B. neotomae is a rodent pathogen and, unlike B. abortus, melitensis, and suis, has not been observed to infect humans. It therefore can be handled more facilely using biosafety level 2 practices. More particularly, using a series of novel fluorescent protein and lux operon reporter systems to differentially label pathogens and track intracellular replication, we confirmed T4SS-dependent intracellular growth of B...
March 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28264908/differences-in-the-importance-of-mast-cells-basophils-ige-and-igg-versus-cd4-t-cells-and-ilc2-cells-in-primary-and-secondary-immunity-to-strongyloides-venezuelensis
#12
Kaori Mukai, Hajime Karasuyama, Kenji Kabashima, Masato Kubo, Stephen J Galli
There is evidence that mast cells, basophils and IgE can contribute to immune responses to parasites, however, the relative importance of these effector elements in parasite immunity is not fully understood. Previous work in Il3-deficient and c-kit mutant Kit(W/W-v) mice indicated that interleukin-3 and c-Kit contribute to expulsion of the intestinal nematode Strongyloides venezuelensis (S.v.) during primary infection. Our findings in mast cell-deficient Kit(W-sh/W-sh) mice and two types of mast cell-deficient mice that have normal c-kit: "Hello Kitty" and MasTRECK mice, confirmed prior work in Kit(W/W-v) mice suggesting that mast cells play an important role in S...
March 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28264907/increased-pilus-production-conferred-by-a-naturally-occurring-mutation-alters-host-pathogen-interaction-in-favor-of-carriage-in-streptococcus-pyogenes
#13
Anthony R Flores, Randall J Olsen, Concepcion Cantu, Kyler B Pallister, Fermin E Guerra, Jovanka M Voyich, James M Musser
Studies of the human pathogen group A Streptococcus (GAS) define the carrier phenotype as increased ability to adhere to and persist on epithelial surfaces and decreased ability to cause disease. We tested the hypothesis that a single amino acid change (Arg135Gly) in a highly conserved sensor kinase (LiaS) of a poorly defined GAS regulatory system contributes to a carrier phenotype through increased pilus production. When introduced into an emm serotype-matched invasive strain, the carrier allele (liaS(R135G)) recapitulated a carrier phenotype defined by increased ability to adhere to mucosal surfaces and decreased ability to cause disease...
March 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28264906/inactivation-of-nmb0419-encoding-a-sel1-like-repeat-slr-protein-in-neisseria-meningitidis-is-associated-with-differential-expression-of-genes-belonging-to-the-fur-regulon-and-reduced-intra-epithelial-replication
#14
Ming-Shi Li, Paul R Langford, J Simon Kroll
Neisseria meningitidis is a commensal microbe that colonizes the human nasopharynx but occasionally invades the bloodstream to cause life-threatening infection. N. meningitidis MC58 NMB0419 encodes a Sel1-like repeat (SLR)-containing protein, previously implicated in invasion of epithelial cells. A gene-regulatory function was revealed in Escherichia coli expressing plasmid-borne NMB0419 showing significantly increased epithelial adherence compared to wild type, due to increased expression of mannose-sensitive type 1 pili...
March 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28264905/perforin-expression-by-cd8-t-cells-is-sufficient-to-cause-fatal-brain-edema-during-experimental-cerebral-malaria
#15
Matthew Huggins, Holly L Johnson, Fang Jin, Aurelie N'Songo, Lisa M Hanson, Stephanie J LaFrance, Noah S Butler, John T Harty, Aaron J Johnson
Human cerebral malaria (HCM) is a serious complication of Plasmodium falciparum infection. The most severe outcomes for patients include coma, permanent neurological deficits, and death. Recently, a large-scale magnetic resonance imaging (MRI) study in humans identified brain swelling as the most prominent predictor of fatal HCM. Therefore, in this study we sought to define the mechanism controlling brain edema through the use of the murine experimental cerebral malaria (ECM) model. Specifically, we investigated the ability of CD8 T cells to initiate brain edema during ECM...
March 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28242621/a-farnesylated-coxiella-burnetii-effector-forms-a-multimeric-complex-at-the-mitochondrial-outer-membrane-during-infection
#16
Laura F Fielden, Jennifer H Moffatt, Yilin Kang, Michael James Baker, Chen Ai Khoo, Craig R Roy, Diana Stojanovski, Hayley J Newton
Coxiella burnetii, the causative agent of Q fever, establishes a unique lysosome-derived intracellular niche termed the Coxiella-containing vacuole (CCV). The Dot/Icm type IVB secretion system is essential for biogenesis of the CCV and intracellular replication of Coxiella. Effector proteins, translocated into the host cell through this apparatus, act to modulate host trafficking and signaling processes to facilitate CCV development. Here we investigated the role of CBU0077, a conserved Coxiella effector that had previously been observed to localize to lysosomal membranes...
February 27, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28223348/immunoactive-clostridial-membrane-vesicle-production-is-regulated-by-a-sporulation-factor
#17
Nozomu Obana, Ryoma Nakao, Kyoko Nagayama, Kouji Nakamura, Hidenobu Senpuku, Nobuhiko Nomura
Recently, many Gram-positive bacteria as well as gram-negative bacteria have been reported to produce MVs, but little is known regarding the regulators involved in MV formation. We found that a Gram-positive anaerobic pathogen, Clostridium perfringens, produces MVs predominantly containing membrane proteins and cell wall components. These MVs stimulated pro-inflammatory cytokine production in mouse macrophage-like cells. We suggested that MVs induced IL-6 production through the TLR2 signaling pathway. Thus, the MV could have a role in the bacteria-host interaction and bacterial infection pathogenesis...
February 21, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28223347/intact-pneumococci-trigger-transcription-of-interferon-related-genes-in-human-monocytes-while-fragmented-autolyzed-bacteria-subvert-this-response
#18
Susann Skovbjerg, Rickard Nordén, Anna Martner, Ebba Samuelsson, Lars Hynsjö, Agnes E Wold
A peculiar trait of pneumococci (Streptococcus pneumoniae) is their propensity to undergo spontaneous lysis during stationary growth due to activation of the enzyme autolysin (LytA) that fragments the peptidoglycan cell wall. The fragments that are generated upon autolysis impair phagocytosis and reduce production of IL-12 and IFN-γ by human leukocytes in response to intact pneumococci, thereby impeding crucial host defenses. The objective was to identify additional monocyte genes whose transcription is induced by intact pneumococci, and subverted by autolyzed bacteria...
February 21, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28223346/chlamydia-trachomatis-cellular-exit-alters-interactions-with-host-dendritic-cells
#19
Ashley M Sherrid, Kevin Hybiske
The strategies utilized by pathogens to exit host cells are an area of pathogenesis which has received surprisingly little attention, considering the necessity of this step for infections to propagate. Even less is known about how exit through these pathways affects downstream host-pathogen interactions and the generation of an immune response. Chlamydia exits host epithelial cells through two equally-active mechanisms: lysis and extrusion. Studies have characterized the outcome of interactions between host innate immune cells such as dendritic cells and macrophages and free, extracellular Chlamydia such as those resulting from lysis...
February 21, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28193635/a-redox-responsive-transcription-factor-is-critical-for-pathogenesis-and-aerobic-growth-of-listeria-monocytogenes
#20
Aaron T Whiteley, Brittany R Ruhland, Mauna B Edrozo, Michelle L Reniere
Bacterial pathogens have evolved sophisticated mechanisms to sense and adapt to redox stress in nature and within the host. However, deciphering the redox environment encountered by intracellular pathogens in the mammalian cytosol is challenging and remains poorly understood. In this study, we assessed the contributions of the two redox-responsive, Spx-family transcriptional regulators to the virulence of Listeria monocytogenes, a Gram-positive facultative intracellular pathogen. Spx-family proteins are highly conserved in Firmicutes and L...
February 13, 2017: Infection and Immunity
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