scholarly journals Actin assembly-inducing protein ActA promotes FcγRIa-mediatedListeriainternalization

2017 ◽  
Author(s):  
Sofya S. Perelman ◽  
Michael E. Abrams ◽  
Neal M. Alto
Keyword(s):  
Listeria Monocytogenes ◽  
Causative Agent ◽  
Cell Invasion ◽  
Immune Defense ◽  
Human Immunoglobulin ◽  
Type I ◽  
Actin Assembly ◽  
Gene Target ◽  
Immunoglobulin Receptor

AbstractListeria monocytogenesis a Gram-positive intracellular pathogen and the causative agent of human listeriosis. While the ability ofL. monocytogenesto enter and survive in professional phagocytes is critical to establish a successful infection, mechanisms of invasion are poorly understood. Our previous investigation into the role of type I interferon-stimulated genes in bacterial infection revealed that the human immunoglobulin receptor FcγRIa served as aL. monocytogenesinvasion factor. FcγRIa-mediatedL. monocytogenesentry occurred independently of immunoglobulin interaction or bacterial internalins. However, the bacterial determinants that mediate FcγRIa interaction remain unclear. Using a comparative genomics approach, we identify actin assembly-inducing protein ActA as a pathogen specific ligand of FcγRIa. FcγRIa enhanced entry of pathogenicL. monocytogenesandL. ivanoviistrain but not non-pathogenicL. innocua. We found that the major virulence regulator PrfA is required for pathogen entry into FcγRIa-expressing cells and identify its gene targetactAas the criticalListerialigand. ActA alone was sufficient to promote entry into FcγRIa-expressing cells, and this function is independent of its actin nucleating activity. Together, these studies present an unexpected role of ActA beyond its canonical function in actin-based motility and expand our understanding ofListeriastrategies for host cell invasion.ImportanceListeria monocytogenesis a food-borne bacterial pathogen and a causative agent of listeriosis with up to 50% mortality rate in immunocompromised individuals. While the mechanisms ofListeriaentry into non-phagocytic cells have been extensively characterized, the details of phagocytic cell invasion are still poorly understood. We have recently discovered that human immunoglobulin receptor FcγRIa mediatesListeriauptake by monocytic cells. This process occurred independently of canonical immunoglobulin interactions as well as classicListeriainternalization factors. Importantly, molecular determinants ofListeria-FcγRIa interaction leading to bacterial entry, remained unknown. In this study, we demonstrate thatListeriavirulence factor actin-assembly inducing protein ActA is required for FcγRIa-mediated entry. Further, ActA was found to be sufficient for the internalization, suggesting its role as a bacterial ligand of FcγRIa. Together, these findings expand our knowledge of mechanisms thatListeriahas evolved to exploit cellular signaling pathways and immune defense of the host.

scholarly journals BIOINFORMATIC SEARCH OF CRISPR/CAS SYSTEM STRUCTURES IN GENOME OF PCT281 PLASMID OF BACILLUS THURINGIENSIS SUBSP. CHINENSIS STRAIN CT-43

2018 ◽  
Vol 3 (5) ◽  
pp. 33-38
Author(s):  
N. A. Arefyeva ◽  
Yu. P. Dzhioev ◽  
A. Yu. Borisenko ◽  
V. I. Chemerilova ◽  
O. F. Vyatchina ◽  
...  
Keyword(s):  
Bacillus Thuringiensis ◽  
Bacterial Genome ◽  
Repeat Sequence ◽  
Immune Defense ◽  
System Structure ◽  
Type I ◽  
Adaptive Immune ◽  
Bacillus Thuringiensis Subsp ◽  
New Information

Background.CRISPR/Cas systems loci are one of the functionally important patterns in bacterial genome which perform the role of “adaptive immune defense” from foreign nucleic acids. The study of CRISPR/Cas systems structure in genomes of plasmids and phages provide new information about the evolution of this systems in bacterial hosts.Aims.A search of CRISPR/Cas systems structures in pCT281 plasmid from Bacillus thuringiensis subsp. chinensis strain CT-43 using bioinformatic methods.Materials and methods.Search studies using bioinformatics methods were performed with the genome of pCT281 plasmid of B. thuringiensis subsp. chinensis strain CT-43 from the RefSeq database. To search for the CRISPR/Cas system structure MacSyFinder (ver. 1.0.5) and three combined algorithms were used: CRISPRFinder; PILER-CR; CRISPR Recognition Tool (CRT). The consensus repeat sequence was generated in WebLogo 3.Results and discussion.In pCT281 plasmid we detected one locus of CRISPR/Cas system of the type I-C which contains 2 CRISPR-cassettes and 4 cas-genes located between them. The CRISPR-cassette 1 includes 10 spacers from 32 to 35 bp and 11 repeats 32bp in length. 5 spacers (33–35 bp) separated by 6 repeats 32 bp in length were detected in the CRISPR-cassette 2.Conclusions.The bioinformatic methods used in this study enable to conduct a search of CRISPR/Cas systems structures in plasmid genomes. The presence of the CRISPR-Cas locus in pCT281 plasmid confirms a possible transfer of this system from the nucleoid to this plasmid. The detected spacers provide information about phages this bacteria was encountered.

Listeria Infections of the Eye

2016 ◽  
Vol 27 (2) ◽  
pp. 115-121 ◽  
Author(s):  
Herbert Hof
Keyword(s):  
Listeria Monocytogenes ◽  
Anterior Chamber ◽  
Causative Agent ◽  
Guinea Pigs ◽  
Specific Therapy ◽  
Ocular Infections ◽  
Exact Diagnosis

The bacterium Listeria monocytogenes resides originally in the environment. Infections of the eye have been induced experimentally; for example, in rabbits and guinea pigs. Natural ocular infections occur in various animals; in most instances, they are induced exogenously; for example, by contaminated silage affecting primarily the conjunctiva, cornea, or the anterior chamber. Sporadic infections as well as outbreaks have been described. In humans, besides exogenous infections, endogenous infections also occur, inducing mainly endophthalmitis. Since an exact diagnosis of the causative agent is often delayed, specific therapy starts too late, so that the outcome is often poor. The antibiotics of primary choice would be ampicillin or a quinolone such as moxifloxacin or levofloxacin. The role of fosfomycin for therapy of ocular infections is discussed.

scholarly journals Mice Lacking the Type I Interferon Receptor Are Resistant to Listeria monocytogenes

2004 ◽  
Vol 200 (4) ◽  
pp. 527-533 ◽  
Author(s):  
Victoria Auerbuch ◽  
Dirk G. Brockstedt ◽  
Nicole Meyer-Morse ◽  
Mary O'Riordan ◽  
Daniel A. Portnoy
Keyword(s):  
Listeria Monocytogenes ◽  
High Dose ◽  
Type I ◽  
Wild Type ◽  
Type I Ifns ◽  
Infection Resistance ◽  
Innate Antiviral Response ◽  
Factor Α

Listeria monocytogenes is a facultative intracellular pathogen that induces a cytosolic signaling cascade resulting in expression of interferon (IFN)-β. Although type I IFNs are critical in viral defense, their role in immunity to bacterial pathogens is much less clear. In this study, we addressed the role of type I IFNs by examining the infection of L. monocytogenes in BALB/c mice lacking the type I IFN receptor (IFN-α/βR−/−). During the first 24 h of infection in vivo, IFN-α/βR−/− and wild-type mice were similar in terms of L. monocytogenes survival. In addition, the intracellular fate of L. monocytogenes in macrophages cultured from IFN-α/βR−/− and wild-type mice was indistinguishable. However, by 72 h after inoculation in vivo, IFN-α/βR−/− mice were ∼1,000-fold more resistant to a high dose L. monocytogenes infection. Resistance was correlated with elevated levels of interleukin 12p70 in the blood and increased numbers of CD11b+ macrophages producing tumor necrosis factor α in the spleen of IFN-α/βR−/− mice. The results of this study suggest that L. monocytogenes might be exploiting an innate antiviral response to promote its pathogenesis.

scholarly journals MON-025 Activin a Increases Human Trophoblast Invasion by Up-Regulating Integrinb1 Through ALK4

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Shiqin Zhu ◽  
Peter C Leung ◽  
Jinlong Ma ◽  
Yan Li
Keyword(s):  
Cell Invasion ◽  
Activin A ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Type I ◽  
Trophoblast Cells ◽  
Integrin Β1 ◽  
Down Regulation ◽  
Human Trophoblast

Abstract Activin A Increases Human Trophoblast Invasion by Up-regulating Integrin β1 Through ALK4 Following implantation, extravillous trophoblast cells (EVTs) derived from trophectoderm invade into the maternal decidua to a certain extent, which is tightly regulated by a variety of factors. Activin A, a member of the TGF-β superfamily, has been shown to stimulate the invasion of human trophoblasts (1). Integrin β1 has been implicated in cancer cell invasion and is consistently expressed in human preimplantation embryos (2). However, whether integrin β1 is integrated in activin A signaling and mediates activin A increased-human trophoblast invasion remain unknown. The objective of our study was to investigate the possible mediation role of integrin β1 in the pro-invasive effect of activin A on trophoblasts and illustrate the underlying molecular mechanisms. Primary and immortalized (HTR8/SVneo) cultures of human trophoblast cells were employed as study models. Real-time qPCR, Western blot, and small interfering RNA (siRNA)-mediated knockdown approaches were used to investigate the molecular determinants of activin A-mediated functions. The integrin β1 protein levels in poorly invasive BeWo,JAR and JEG-3 human choriocarcinoma cells were lower than that in highly invasive HTR8/SVneo cells and primary human EVTs, suggesting the possible essential role of integrin β1 in mediating human trophoblast invasion. The expression levels of integrin β1 were up-regulated in a time-dependent manner after activin A treatment in HTR8/SVneo cells. Importantly, siRNA-mediated down-regulation of integrin β1 significantly attenuated both basal and activin A-induced cell invasion in HTR8/SVneo cells as measured by transwell invasion assay. Interestingly, the TGF-β type I receptors (ALK4/5/7) inhibitor SB431542 abolished activin A-induced activation of SMAD2/SMAD3 as well as activin A-up-regulated integrin 1 expression. Moreover, siRNA-mediated down-regulation of ALK4 or SMAD4 attenuated activin A-up-regulated integrin β1 in both HTR8/SVneo cells and human primary EVT cells. These results reveal that activin A promotes human trophoblast cell invasion by up-regulating integrin β1 expression through ALK4-activated SMAD2/3-SMAD4 signaling pathway. Reference: (1) Bearfield et al., Eur J Endocrinol 2005;152:909–16. (2) Campbell et al., Hum Reprod 1995;10:1571–8.

scholarly journals The Role of Type I IFNs in Influenza: Antiviral Superheroes or Immunopathogenic Villains?

2020 ◽  
Vol 12 (6) ◽  
pp. 437-447 ◽  
Author(s):  
Wenxin Wu ◽  
Jordan P. Metcalf
Keyword(s):  
Influenza A ◽  
Cell Function ◽  
Influenza Infection ◽  
Immune Defense ◽  
Type I ◽  
Type I Ifns ◽  
Infection Treatment ◽  
Individual Host ◽  
The Individual

The important role of interferons (IFNs) in antiviral innate immune defense is well established. Although recombinant IFN-α was approved for cancer and chronic viral infection treatment by regulatory agencies in many countries starting in 1986, no IFNs are approved for treatment of influenza A virus (IAV) infection. This is partially due to the complex effects of IFNs in acute influenza infection. IAV attacks the human respiratory system and causes significant morbidity and mortality globally. During influenza infection, depending on the strain of IAV and the individual host, type I IFNs can have protective antiviral effects or can contribute to immunopathology. In the context of virus infection, the immune system has complicated mechanisms regulating the expression and effects of type I IFN to maximize the antiviral response by both activating and enhancing beneficial innate cell function, while limiting immunopathological responses that lead to exaggerated tissue damage. In this review, we summarize the complicated, but important, role of type I IFNs in influenza infections. This includes both protective and harmful effects of these important cytokines during infection.

scholarly journals Listeria monocytogenes Flagella Are Used for Motility, Not as Adhesins, To Increase Host Cell Invasion

2006 ◽  
Vol 74 (12) ◽  
pp. 6675-6681 ◽  
Author(s):  
Heather S. O'Neil ◽  
Hélène Marquis
Keyword(s):  
Listeria Monocytogenes ◽  
Cell Invasion ◽  
Early Time ◽  
Host Cells ◽  
Host Cell Invasion ◽  
Time Points ◽  
Food Borne ◽  
Epithelial Cell Invasion

ABSTRACT Flagellar structures contribute to the virulence of multiple gastrointestinal pathogens either as the effectors of motility, as adhesins, or as a secretion apparatus for virulence factors. Listeria monocytogenes is a food-borne, gram-positive pathogen that uses flagella to increase the efficiency of epithelial cell invasion (A. Bigot, H. Pagniez, E. Botton, C. Frehel, I. Dubail, C. Jacquet, A. Charbit, and C. Raynaud, Infect. Immun. 73:5530-5539, 2005; L. Dons, E. Eriksson, Y. Jin, M. E. Rottenberg, K. Kristensson, C. N. Larsen, J. Bresciani, and J. E. Olsen, Infect. Immun. 72:3237-3244, 2004). In this study, we aimed to elucidate the mechanism by which flagella contribute to L. monocytogenes invasion. To examine the role of flagella as adhesins, invasion and adhesion assays were performed with flagellated motile and nonmotile bacteria and nonflagellated bacteria. We observed that flagellated but nonmotile bacteria do not adhere to or invade human epithelial cells more efficiently than nonflagellated bacteria. These results indicated that flagella do not function as adhesins to enhance the adhesion of L. monocytogenes to targeted host cells. Instead, it appears that motility is important for tissue culture invasion. Furthermore, we tested whether motility contributes to early colonization of the gastrointestinal tract using a competitive index assay in which mice were infected orally with motile and nonmotile bacteria in a 1:1 ratio. Differential bacterial counts demonstrated that motile bacteria outcompete nonmotile bacteria in the colonization of the intestines at early time points postinfection. This difference is also reflected in invasion of the liver 12 h later, suggesting that flagellum-mediated motility enhances L. monocytogenes infectivity soon after bacterial ingestion in vivo.

scholarly journals Listeriolysin O-Mediated Calcium Influx Potentiates Entry of Listeria monocytogenes into the Human Hep-2 Epithelial Cell Line

2003 ◽  
Vol 71 (6) ◽  
pp. 3614-3618 ◽  
Author(s):  
Shaynoor Dramsi ◽  
Pascale Cossart
Keyword(s):  
Listeria Monocytogenes ◽  
Epithelial Cell ◽  
Cell Line ◽  
Cell Invasion ◽  
Mammalian Cells ◽  
Calcium Influx ◽  
Epithelial Cell Line ◽  
Listeriolysin O ◽  
Calcium Channel Antagonists

ABSTRACT To investigate factors which modulate the entry of Listeria monocytogenes into mammalian cells, we have analyzed the role of Ca2+. We show that L. monocytogenes induced Ca2+ transients into the human Hep-2 epithelial cell line. The nonpathogenic species L. innocua or a L. monocytogenes mutant strain defective in listeriolysin O (LLO) production was unable to induce these calcium fluxes. Addition of plasma membrane calcium channel antagonists or chelation of extracellular calcium markedly reduced L. monocytogenes entry. In contrast, chelation of host cytosolic Ca2+ or blockade of Ca2+ release from intracellular stores did not affect invasion. These results indicate that L. monocytogenes-induced mobilization of extracellular Ca2+ by LLO and activation of downstream Ca2+-dependent signaling are required for efficient cell invasion.

scholarly journals Distinct vitellogenin domains differentially regulate immunological outcomes in invertebrates

2020 ◽  
pp. jbc.RA120.015686
Author(s):  
Weikang Sun ◽  
Hao Li ◽  
Yuehong Zhao ◽  
Longwei Bai ◽  
Yukai Qin ◽  
...  
Keyword(s):  
Eriocheir Sinensis ◽  
Binding Activity ◽  
Immune Defense ◽  
Amino Acid Residues ◽  
Research Attention ◽  
Immunoglobulin Receptor ◽  
Bacterial Binding ◽  
Mitten Crab ◽  
New Evidence

The classical role of Vitellogenin (Vg) is providing energy reserves for developing embryos, but its roles appear to extend beyond this nutritional function, and its importance in host immune defense is garnering increasing research attention. However, Vg-regulated immunological functions are dependent on three different domains within different species and remain poorly understood. In the present study, we confirmed three conserved VG domains — LPD_N, DUF1943 and VWD — in the Chinese mitten crab (Eriocheir sinensis), highlighting functional similarities of Vg in vertebrates and invertebrates. Of these three domains, DUF1943 and VWD showed definitive bacterial binding activity via interaction with the signature components on microbial surfaces, but this activity was s not exhibited by the LPD_N domain. Antibacterial assays indicated that only the VWD domain inhibits bacterial proliferation, and this function may be conserved between different species due to the conserved amino acid residues. To further explore the relationship between Vg and polymeric immunoglobulin receptor (pIgR), we expressed EspIgR and the three Eriocheir sinensis-Vg (EsVg) domains in HEK293T cells, and co-immunoprecipitation assay demonstrated that only the DUF1943 domain interacts with EspIgR. Subsequent experiments demonstrated that EsVg regulates hemocyte phagocytosis by binding with EspIgR through the DUF1943 domain, thus promoting bacterial clearance and protecting the host from bacterial infection. To the best of our knowledge, our work is the first to report distinct domains in Vg inducing different immunological outcomes in invertebrates, providing new evidence that pIgR acts as a phagocytic receptor for Vg.

Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice

2000 ◽  
Vol 12 (12) ◽  
pp. 4447-4456 ◽  
Author(s):  
Rose-Marie Bluthe ◽  
Sophie Laye ◽  
Bruno Michaud ◽  
Chantal Combe ◽  
Robert Dantzer ◽  
...  
Keyword(s):  
Tumour Necrosis ◽  
Interleukin 1 ◽  
Tumour Necrosis Factor Alpha ◽  
Type I ◽  
Sickness Behaviour ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Deficient Mice ◽  
Necrosis Factor
Sign in / Sign up

Export Citation Format

Share Document