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Infection and Immunity

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https://www.readbyqxmd.com/read/28223348/immunoactive-clostridial-membrane-vesicle-production-is-regulated-by-a-sporulation-factor
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28193634/purified-streptococcus-pneumoniae-endopeptidase-o-pepo-enhances-particle-uptake-by-macrophages-in-a-tlr2-and-mir-155-dependent-manner
#5
Hua Yao, Hong Zhang, Kai Lan, Hong Wang, Yufeng Su, Dagen Li, Zhixin Song, Fang Cui, Yibing Yin, Xuemei Zhang
Insights into the host-microbial virulence factors interaction, especially the immune-signaling mechanisms, could provide novel prevention and treatment options for pneumococcal diseases. Streptococcus pneumoniae endopeptidase O (PepO) is a newly discovered and ubiquitously expressed pneumococcal virulence protein. A PepO-mutant strain showed impaired adherence to and invasion of host cells compared with their isogenic wild-type strains. It is still unknown whether PepO is involved in host defense response against pneumococcal infection...
February 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28167672/anthelmintic-therapy-modifies-the-systemic-and-mycobacterial-antigen-stimulated-cytokine-profile-in-helminth-latent-mycobacterium-tuberculosis-co-infection
#6
Rajamanickam Anuradha, Saravanan Munisankar, Yukthi Bhootra, Chandrakumar Dolla, Paul Kumaran, Thomas B Nutman, Subash Babu
Helminth infections are known to modulate cytokine responses in latent tuberculosis (LTB). However, very few studies have examined whether this modulation is reversible upon anthelmintic therapy. We measured the systemic and mycobacterial (TB) - antigen-stimulated levels of Type 1, Type 2, Type 17 and regulatory cytokines in individuals with LTB and with or without coexistent Strongyloides stercoralis (Ss) infection before and after anthelmintic therapy. Our data reveal that individuals with LTB and coexistent Ss infection have significantly lower levels of systemic and TB antigen-stimulated Type 1 (IFNγ, TNFα and IL-2) and Type 17 (IL-17A and/or IL-17F) cytokines and significantly higher levels of systemic but not TB antigen-stimulated Type 2 (IL-4 and IL-5) and regulatory (TGFβ) cytokines...
February 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28167671/defining-the-ail-ligand-binding-surface-hydrophobic-residues-in-two-extracellular-loops-mediate-cell-and-extracellular-matrix-binding-to-facilitate-yop-delivery
#7
Tiffany M Tsang, Jeffrey S Wiese, Jamal A Alhabeil, Lisa D Usselman, Joshua J Thomson, Rafla Matti, Malte Kronshage, Natalie Maricic, Shanedah Williams, Naama H Sleiman, Suleyman Felek, Eric S Krukonis
Yersinia pestis, the causative agent of plague, binds host cells to deliver cytotoxic Yop proteins into the cytoplasm that prevent phagocytosis and generation of pro-inflammatory cytokines. Ail is an eight-stranded β-barrel outer membrane protein with four extracellular loops that mediates cell binding and resistance to human serum. Following deletion of each of the four extracellular loops that potentially interact with host cells, the Ail-Δloop 2 and Ail-Δloop 3 mutants had no cell binding activity while Ail-Δloop 4 maintained cell binding (the Ail-Δloop 1 protein was unstable)...
February 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28167670/salmonella-typhi-lipopolysaccharide-o-antigen-modifications-impact-on-serum-resistance-and-antibody-recognition
#8
Erica Kintz, Christian Heiss, Ian Black, Nicholas Donohue, Naj Brown, Mark R Davies, Parastoo Azadi, Stephen Baker, Paul M Kaye, Marjan van der Woude
Salmonella Typhi is a human restricted Gram-negative bacterial pathogen, responsible for causing an estimated 27 million cases of typhoid fever annually leading to 217,000 deaths, and current vaccines do not offer full protection. The O-antigen side chain of the lipopolysaccharide is an immunodominant antigen, can define host-pathogen interactions, and is under consideration as a vaccine target for some Gram-negative species. The composition of the O-antigen can be modified by activity of glycosyltransferase (gtr) operons acquired by horizontal gene transfer...
February 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28167669/mucosal-antibodies-to-the-c-terminus-of-toxin-a-prevent-colonization-of-clostridium-difficile
#9
Huynh A Hong, Krisztina Hitri, Siamand Hosseini, Natalia Kotowicz, Donna Bryan, Fatme Mawas, Anthony J Wilkinson, Annie van Broekhoven, Jonathan Kearsey, Simon M Cutting
Mucosal immunity is considered important for protection to Clostridium difficile infection (CDI). We show that in hamsters immunized with Bacillus subtilis spores expressing a carboxy-terminal segment (TcdA26-39) of C. difficile toxin A no colonization occurs in protected animals when challenged with C. difficile strain 630. By contrast, animals immunized with toxoids showed no protection and remained fully colonized. As well as neutralizing toxins, antibodies to TcdA26-39 (but not to toxoids), whether raised to the recombinant protein, or to TcdA26-39 expressed on the B...
February 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28167668/myeloid-specific-knockout-of-nfi-a-improves-sepsis-survival
#10
Melissa B McPeak, Dima Youssef, Danielle A Williams, Christopher Pritchett, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar
Myeloid-derived suppressor cells (MDSCs) arise from myeloid progenitors and suppress both innate and adaptive immunity. MDSCs expand during the later phases of sepsis in mice, promote immunosuppression, and reduce survival. Here, we report that the myeloid differentiation-related transcription factor NFI-A controls MDSC expansion during sepsis and impacts survival. Unlike MDSCs, myeloid cells with conditional deletion of the Nfia normally differentiated into effector cells during sepsis, cleared infecting bacteria, and did not express immunosuppressive mediators...
February 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28167667/the-protective-role-of-passively-transferred-maternal-cytokines-against-bordetella-pertussis-infection-in-newborn-piglets
#11
Shokrollah Elahi, David R Thompson, Jill Van Kessel, Lorne A Babiuk, Volker Gerdts
Maternal vaccination represents a potential strategy to protect both the mother and the offspring against life threatening infections. This protective role has mainly been associated with antibodies but the role of cell mediated immunity in particular passively transferred cytokines is not well understood. Herein, using a pertussis model we have demonstrated that immunization of pregnant sows with heat-inactivated bacteria leads to induction of a wide range of cytokines (e.g. TNF-α, IFN-γ, IL-6, IL-8 and IL-12/IL-23p40) in addition to pertussis-specific antibodies...
February 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28138025/activity-of-the-pore-forming-virulence-factor-listeriolysin-o-is-reversibly-inhibited-by-naturally-occurring-s-glutathionylation
#12
Jonathan L Portman, Qiongying Huang, Michelle L Reniere, Anthony T Iavarone, Daniel A Portnoy
Cholesterol-dependent cytolysins (CDCs) represent a family of homologous pore-forming proteins secreted by many Gram-positive bacterial pathogens. CDCs mediate membrane binding partly through a conserved C-terminal undecapeptide, which contains a single cysteine residue. While mutational changes to other residues in the undecapeptide typically have severe effects, mutating the cysteine residue to alanine has minor effects on overall protein function. Thus, the function of this highly conserved reactive cysteine residue remains largely unknown...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28138024/oxyr2-modulates-oxyr1-activity-and-vibrio-cholerae-oxidative-stress-response
#13
Hui Wang, Nawar Naseer, Yaran Chen, Anthony Y Zhu, Xuewen Kuai, Nirupa Galagedera, Zhi Liu, Jun Zhu
Bacteria have developed capacities to deal with different stresses and adapt to different environmental niches. The human pathogen Vibrio cholerae, the causative agent of severe diarrheal disease cholera, utilizes the transcriptional regulator OxyR to activate genes related to oxidative stress resistance, including peroxiredoxin PrxA, in response to hydrogen peroxide. In this study, we identified another OxyR homolog in V. cholerae, which we named OxyR2 and renamed the previous OxyR as OxyR1. We found that OxyR2 is required to activate its divergently transcribed gene ahpC, encoding an alkylhydroperoxide reductase, independent of H2O2 A conserved cysteine residue in OxyR2 is critical for this function...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28138023/distinct-roles-of-the-anti-apoptotic-effectors-nleb-and-nlef-from-enteropathogenic-escherichia-coli
#14
Georgina L Pollock, Clare V L Oates, Cristina Giogha, Tania Wong Fok Lung, Sze Ying Ong, Jaclyn S Pearson, Elizabeth L Hartland
During infection, enteropathogenic Escherichia coli (EPEC) translocates effector proteins directly into the cytosol of infected enterocytes using a type III secretion system (T3SS). Once inside the host cell, these effector proteins subvert various immune signaling pathways including death receptor-induced apoptosis. One such effector protein is the Non-LEE encoded effector NleB1, which inhibits extrinsic apoptotic signaling via the FAS death receptor. NleB1 transfers a single GlcNAc residue to Arg117 in the death domain of FADD and inhibits FAS ligand (FasL) stimulated caspase-8 cleavage...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28138022/the-severity-of-plasmodium-falciparum-infection-is-associated-with-transcript-levels-of-var-genes-encoding-epcr-binding-pfemp1
#15
Sixbert I Mkumbaye, Christian W Wang, Eric Lyimo, Jakob S Jespersen, Alphaxard Manjurano, Jacklin Mosha, Reginald A Kavishe, Steven B Mwakalinga, Daniel T R Minja, John P Lusingu, Thor G Theander, Thomas Lavstsen
By attaching infected erythrocytes to the vascular lining, Plasmodium falciparum parasites leave blood circulation and avoid splenic clearance. This sequestration is central to pathogenesis. Severe malaria is associated with parasites expressing an antigenically distinct subset of P. falciparum erythrocyte membrane protein 1 (PfEMP1) mediating the binding to endothelial receptors. Previous studies indicate that PfEMP1, with so-called CIDRα1 domains capable of binding endothelial protein C receptor (EPCR), constitute the PfEMP1 subset associated with severe paediatric malaria...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28138021/co-infection-of-helicobacter-pylori-and-opisthorchis-viverrini-enhances-the-severity-of-hepatobiliary-abnormalities-in-hamsters
#16
Rungtiwa Dangtakot, Somchai Pinlaor, Upsornsawan Itthitaetrakool, Apisit Chaidee, Chariya Chomvarin, Arunnee Sangka, Chotechana Wilailuckana, Porntip Pinlaor
Persistent infection with Opisthorchis viverrini causes hepatobiliary abnormalities, predisposing infected individuals to cholangiocarcinoma (CCA). In addition, Helicobacter pylori is highly prevalent in most countries and is a possible risk factor for CCA; however, its role in enhancing hepatobiliary abnormality is unclear. Here, we investigated the effects of co-infection of H. pylori and O. viverrini on hepatobiliary abnormality. Hamsters were divided into four groups: (1) normal, (2) H. pylori-infected (HP), (3) O...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28138020/the-type-ii-secretion-system-of-legionella-pneumophila-dampens-the-myd88-and-tlr2-signaling-pathway-in-infected-human-macrophages
#17
Celeste A Mallama, Kessler McCoy-Simandle, Nicholas P Cianciotto
Previously, we reported that mutants of L. pneumophila lacking a type II secretion (T2S) system elicit higher levels of cytokines (e.g., IL-6) following infection of U937 cells, a human macrophage-like cell line. We now show that this effect of T2S is also manifest upon infection of human THP-1 cell macrophages and peripheral blood monocytes but does not occur during infection of murine macrophages. Supporting the hypothesis that T2S acts to dampen the triggering of an innate immune response, we observed that the mitogen-activated protein kinase (MAPK) and nuclear transcription factor kappa-B (NF-κB) pathways are more highly stimulated upon infection with the T2S mutant compared to wild-type...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28138019/involvement-of-host-defense-mechanisms-against-toxoplasma-gondii-infection-in-anhedonic-and-despair-like-behaviors-in-mice
#18
Motamed E Mahmoud, Ragab Fereig, Yoshifumi Nishikawa
Toxoplasma gondii is a pathogen relevant to psychiatric disorders. We recently showed that reactivation of chronic T. gondii induced depressive-like behaviors in mice. Further, it has been hypothesized that depression-like behaviors are mediated via a host defense mechanism against invading pathogens; proximate mechanisms of this behavioral hypothesis remain unclear. In the present study, we investigate the contribution of indoleamine 2, 3-dioxygenase (IDO), inflammation and interferon-gamma (IFN-γ) on anhedonic- and despair-related behaviors in T...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28138018/cellular-uptake-of-clostridium-botulinum-c2-toxin-requires-acid-sphingomyelinase-activity
#19
Masahiro Nagahama, Masaya Takehara, Teruhisa Takagishi, Soshi Seike, Kazuaki Miyamoto, Keiko Kobayashi
Clostridium botulinum C2 toxin consists of an enzyme component (C2I) and a binding component (C2II). Activated C2II (C2IIa) binds to a cell receptor, giving rise to lipid raft-dependent oligomerization, and then it assembles with C2I. The whole toxin complex is then endocytosed into the cytosol, resulting in destruction of the actin cytoskeleton and cell rounding. Here, we showed that C2 toxin requires acid sphingomyelinase (ASMase) activity during internalization. In this study, inhibitors of ASMase and lysosomal exocytosis blocked C2 toxin-induced cell rounding...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28115509/the-tat-substrate-sufi-is-critical-for-the-ability-of-yersinia-pseudotuberculosis-to-cause-systemic-infection
#20
Ummehan Avican, Tugrul Doruk, Yngve Östberg, Anna Fahlgren, Åke Forsberg
The Twin-arginine translocation (Tat) system targets folded proteins across the inner membrane and it is crucial for virulence in many important human pathogenic bacteria. Tat has been shown to be required for virulence of Yersinia pseudotuberculosis and we recently showed that the system is critical for different virulence related stress responses as well as for iron uptake. In this study, we wanted to address the role of the Tat substrates in in vivo virulence. Therefore, 22 genes encoding potential Tat substrates were mutated and each mutant was evaluated in competitive oral infection of mice...
January 23, 2017: Infection and Immunity
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