Table of Contents

Volume 3, Issue 7

  November 15, 2012

  Pages 551 - 694

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Virulence: Three years and counting

Eva M. Riedmann and Eleftherios Mylonakis
Pages 551 - 552
http://dx.doi.org/10.4161/viru.23252
Full Text | PDF

The streptococcal hemoprotein receptor: A moonlighting protein or a virulence factor?

Zehava Eichenbaum
Pages 553 - 555
http://dx.doi.org/10.4161/viru.22440
Abstract | Full Text | PDF

The β-hemolytic group A streptococcus (GAS) is a major pathogen that readily uses hemoglobin to satisfy its requirements for iron. The streptococcal hemoprotein receptor in GAS plays a central role in heme utilization and binds fibronectin and laminin in vitro. Shr inactivation attenuates the virulent M1T1 GAS strain in two murine infection models and reduces bacterial growth in blood and binding to laminin. Shr impact on the globally disseminated M1T1 strain underscores the importance of heme uptake in GAS pathogenesis and raises the possibility of targeting heme-uptake proteins in the development of new methods to combat GAS infections.




REVIEW

Open Access Article

Phage-bacterial interactions in the evolution of toxigenic Vibrio cholerae

Shah M. Faruque and John J. Mekalanos
Pages 556 - 565
http://dx.doi.org/10.4161/viru.22351
Abstract | Full Text | PDF

Understanding the genetic and ecological factors which support the emergence of new clones of pathogenic bacteria is vital to develop preventive measures. Vibrio cholerae the causative agent of cholera epidemics represents a paradigm for this process in that this organism evolved from environmental non-pathogenic strains by acquisition of virulence genes. The major virulence factors of V. cholerae, cholera toxin (CT) and toxin coregulated pilus (TCP) are encoded by a lysogenic bacteriophage (CTXφ) and a pathogenicity island, respectively. Additional phages which cooperate with the CTXφ in horizontal transfer of genes in V. cholerae have been characterized, and the potential exists for discovering yet new phages or genetic elements which support the transfer of genes for environmental fitness and virulence leading to the emergence of new epidemic strains. Phages have also been shown to play a crucial role in modulating seasonal cholera epidemics. Thus, the complex array of natural phenomena driving the evolution of pathogenic V. cholerae includes, among other factors, phages that either participate in horizontal gene transfer or in a bactericidal selection process favoring the emergence of new clones of V. cholerae.




RESEARCH PAPER

Study of streptococcal hemoprotein receptor (Shr) in iron acquisition and virulence of M1T1 group A streptococcus

Samira Dahesh, Victor Nizet and Jason N. Cole
Pages 566 - 575
http://dx.doi.org/10.4161/viru.21933
Abstract | Full Text | PDF

Streptococcus pyogenes (group A streptococcus, GAS) is a human bacterial pathogen of global significance, causing severe invasive diseases associated with serious morbidity and mortality. To survive within the host and establish an infection, GAS requires essential nutrients, including iron. The streptococcal hemoprotein receptor (Shr) is a surface-localized GAS protein that binds heme-containing proteins and extracellular matrix components. In this study, we employ targeted allelic exchange mutagenesis to investigate the role of Shr in the pathogenesis of the globally disseminated serotype M1T1 GAS. The shr mutant exhibited a growth defect in iron-restricted medium supplemented with ferric chloride, but no significant differences were observed in neutrophil survival, antimicrobial peptide resistance, cell surface charge, fibronectin-binding or adherence to human epithelial cells and keratinocytes, compared with wild-type. However, the shr mutant displayed a reduction in human blood proliferation, laminin-binding capacity and was attenuated for virulence in in vivo models of skin and systemic infection. We conclude that Shr augments GAS adherence to laminin, an important extracellular matrix attachment component. Furthermore, Shr-mediated iron uptake contributes to GAS growth in human blood, and is required for full virulence of serotype M1T1 GAS in mouse models of invasive disease.




BRIEF REPORT

Community-associated and healthcare-associated methicillin-resistant Staphylococcus aureus virulence toward Caenorhabditis elegans compared

Shandra R. Day, Christopher M. Moore, John R. Kundzins and Costi D. Sifri
Pages 576 - 582
http://dx.doi.org/10.4161/viru.22120
Abstract | Full Text | PDF

Community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged as major human pathogens. CA-MRSA virulence appears to be distinct from healthcare-associated (HA) MRSA with several factors [α-hemolysin (Hla), Panton-Valentine leukocidin (PVL), α-type phenol soluble modulins (PSMα) and SCCmec IV] postulated to enhance virulence or fitness. Using the Caenorhabditis elegans infection model, we compared the virulence of clinical and laboratory isolates of CA-MRSA and HA-MRSA and explored the contribution of CA-MRSA associated virulence factors to nematode killing. All CA-MRSA strains were highly pathogenic to nematodes, while HA-MRSA strains demonstrated variable nematode killing. Nematode killing by isogenic mutants of hla or the loci for PVL, PSMα, PSMβ, PSMδ or SCCmec IV was not different than the parental strains. These results demonstrate that CA-MRSA is highly virulent, shows some strains of HA-MRSA are equally virulent toward nematodes and suggests CA-MRSA virulence in C. elegans is not linked to a single virulence factor.




PERSPECTIVE

Open Access Article

Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome

Carol U. Meteyer, Daniel Barber and Judith N. Mandl
Pages 583 - 588
http://dx.doi.org/10.4161/viru.22330
Abstract | Full Text | PDF

White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at the site of fungal infection and erosion is consistent with a temperature-induced inhibition of immune cell trafficking. This immune suppression allows G. destructans to colonize and erode the skin of wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks of emergence from hibernation an intense neutrophilic inflammatory response to G. destructans is generated, causing severe pathology that can contribute to death. We hypothesize that the sudden reversal of immune suppression in bats upon the return to euthermia leads to a form of immune reconstitution inflammatory syndrome (IRIS). IRIS was first described in HIV-infected humans with low helper T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a paradoxical and rapid worsening of symptoms in immune compromised humans upon restoration of immunity in the face of an ongoing infectious process. In humans with HIV, the restoration of adaptive immunity following suppression of HIV replication with anti-retroviral therapy (ART) can trigger severe immune-mediated tissue damage that can result in death. We propose that the sudden restoration of immune responses in bats infected with G. destructans results in an IRIS-like dysregulated immune response that causes the post-emergent pathology.




NEWS AND VIEWS

Open Access Article

Deformed wing virus: The main suspect in unexplained honeybee deaths worldwide

Declan C. Schroeder and Stephen J. Martin
Pages 589 - 591
http://dx.doi.org/10.4161/viru.22219
Full Text | PDF

Open Access Article

Molecular blueprint of uropathogenic Escherichia coli virulence provides clues toward the development of anti-virulence therapeutics

Maria Kostakioti, Scott J. Hultgren and Maria Hadjifrangiskou
Pages 592 - 593
http://dx.doi.org/10.4161/viru.22364
Full Text | PDF

Open Access Article

Turning up Francisella pathogenesis: The LPS thermostat

Daniel A. Powell, Yanyan Li and Robert K. Ernst
Pages 594 - 595
http://dx.doi.org/10.4161/viru.22496
Full Text | PDF

Open Access Article

The fate of not sensing phosphate: Downregulation of type 1 fimbriae through activation of the Pho regulon reduces E. coli urinary tract virulence

Sébastien Crépin, Gaëlle Porcheron, Josée Harel and Charles M. Dozois
Pages 596 - 598
http://dx.doi.org/10.4161/viru.22539
Full Text | PDF




LETTER TO THE EDITOR

The girl with the iron tattoo

Sophia Fircanis, Reve Shields, Jorge Castillo, Anthony Mega and Fred Schiffman
Pages 599 - 600
http://dx.doi.org/10.4161/viru.22122
Abstract | Full Text | PDF

We describe a young woman with profound anemia whose serum iron studies were incongruous with what we expected from iron deficiency anemia. Her high serum iron was not fully explainable until we examined the patient and noticed a large black tattoo on her left flank area. Apparently iron oxide in the ink used for the tattoo was absorbed transcutaneously and led to high serum iron in the face of the other data, which suggested iron deficiency. She was slow in mobilizing her serum iron for erythropoiesis and we discovered that there was a concurrent acute B19 parvovirus infection, which impeded utilization of the iron for red blood cell production. We believe that this case report reinforces the imperative to always do a careful physical examination with any patient who has anemia, and also illustrates the potential toxicity of tattoo ink. The impairment of utilization of the serum iron because of the patient's acute B19 parvovirus infection demonstrates the many consequences of infection induced aplastic anemia.





Special Focus: Dendritic Cells

EDITORIAL

Open Access Article

The dendritic cell: The general of the army

Jatin M. Vyas
Pages 601 - 602
http://dx.doi.org/10.4161/viru.22975
Full Text | PDF

REVIEWS

Open Access Article

Dendritic cells and influenza A virus infection

Jason Waithman and Justine D. Mintern
Pages 603 - 608
http://dx.doi.org/10.4161/viru.21864
Abstract | Full Text | PDF

Influenza A virus (IAV) is a dangerous virus equipped with the potential to evoke widespread pandemic disease. The 2009 H1N1 pandemic highlights the urgency for developing effective therapeutics against IAV infection. Vaccination is a major weapon to combat IAV and efforts to improve current regimes are critically important. Here, we will review the role of dendritic cells (DCs), a pivotal cell type in the initiation of robust IAV immunity. The complexity of DC subset heterogeneity in the respiratory tract and lymph node that drains the IAV infected lung will be discussed, together with the varied and in some cases, conflicting contributions of individual DC populations to presenting IAV associated antigen to T cells.

Open Access Article

Dendritic cells, regulatory T cells and the pathogenesis of chronic hepatitis C

Phyllis T. Losikoff, Alyssa A. Self and Stephen H. Gregory
Pages 610 - 620
http://dx.doi.org/10.4161/viru.21823
Abstract | Full Text | PDF

Hepatitis C virus (HCV) is a small, enveloped RNA virus and a major cause of chronic liver disease. Resolution of primary HCV infections depends upon the vigorous responses of CD4⁺ and CD8⁺ T cells to multiple viral epitopes. Although such broad-based responses are readily detected early during the course of infection regardless of clinical outcome, they are not maintained in individuals who develop chronic disease. Ostensibly, a variety of factors contribute to the diminished T cell responses observed in chronic, HCV-infected patients including impaired dendritic cell function and the induction of CD4⁺FoxP3⁺ regulatory T cells. Overwhelming evidence suggests that the complex interaction of dendritic cells and regulatory T cells plays a critical role in the pathogenesis of chronic hepatitis C.

Open Access Article

Dendritic cell biology in human cytomegalovirus infection and the clinical consequences for host immunity and pathology

Sara Gredmark-Russ and Cecilia Söderberg-Nauclér
Pages 621 - 634
http://dx.doi.org/10.4161/viru.22239
Abstract | Full Text | PDF

Human cytomegalovirus (HCMV), a member of the herpesvirus family, establishes life-long persistence and latency after primary infection and can be reactivated later in life. In immunosuppressed patients, it is an important pathogen that can cause severe disease. HCMV is also thought to play a causative role in inflammatory diseases and cancer. The virus can infect different immune cells, including dendritic cells (DCs) and can take advantage of host immune functions to avoid immune recognition. These characteristics have sparked major interest in understanding HCMV and its interaction with immune cells and their relevance to disease pathogenesis. In this review, we focus on the complex host-pathogen relationship between HCMV and DCs, including the persistence of the virus in these cells, their function in the immune response to HCMV infection and the potential clinical consequences of HCMV infection in DCs.

Open Access Article

The role of dendritic cells in the innate recognition of pathogenic fungi (A. fumigatus, C. neoformans and C. albicans)

Zaida G. Ramirez-Ortiz and Terry K. Means
Pages 635 - 646
http://dx.doi.org/10.4161/viru.22295
Abstract | Full Text | PDF

Dendritic cells (DCs) are the bridge between the innate and adaptive immune system. DCs are responsible for sensing and patrolling the environment, initiating a host response and instructing the proper adaptive immune response against pathogens. Recent advances in medical treatments have led to increased use of immunosuppressive drugs, leading to the emergence of fungal species that cause life-threatening infections in humans. Three of these opportunistic fungal pathogens: Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans pose the biggest concern for the immune-compromised host. Here we will review the interactions between DCs and these fungal pathogens, the receptors expressed on DCs that mediate these responses and the signaling mechanisms that shape the adaptive host response.

Open Access Article

A dendrite in every pie: Myeloid dendritic cells in HIV and SIV infection

Elizabeth R. Wonderlich and Simon M. Barratt-Boyes
Pages 647 - 653
http://dx.doi.org/10.4161/viru.22491
Abstract | Full Text | PDF

Dendritic cells (DC) are a heterogeneous population of innate immune cells that are fundamental to initiating responses against invading pathogens and regulating immune responses. Myeloid DC (mDC) act as a bridge between the innate and adaptive immune response during virus infections but their role in immunity to human immunodeficiency virus (HIV) remains ill-defined. This review examines aspects of the mDC response to HIV and its simian counterpart, simian immunodeficiency virus (SIV), and emphasizes areas where our knowledge of mDC biology and function is incomplete. Defining the potentially beneficial and detrimental roles mDC play during pathogenic and stable infection of humans and nonhuman primates is crucial to our overall understanding of AIDS pathogenesis.

Open Access Article

The role of dendritic cells in Mycobacterium tuberculosis infection

Adane Mihret
Pages 654 - 659
http://dx.doi.org/10.4161/viru.22586
Abstract | Full Text | PDF

The immune response against Mycobacterium tuberculosis is multifactorial, involving a network of innate and adaptive immune responses. Characterization of the immune response, a clear understanding of the dynamics and interplay of different arms of the immune response are critical to allow the development of better tools for combating tuberculosis. Dendritic cells (DCs) are one of the key cells in bridging innate and adaptive immune response through their significant role in capturing, processing and presenting antigens. The outcome of interaction of M. tuberculosis with DCs is not fully understood and the available reports are contradictory were some findings reported that DCs strengthen the cellular immune response against mycobacterium infection whereas others reported M. tuberculosis impairs the function of DCs were infected DCs are poor stimulators of M. tuberculosis Ag-specific CD4 T cells. Other studies showed that the outcome depends on M. tuberculosis strain type and type of receptor on DCs during recognition. In this review I shall highlight the recent findings in the outcome of interaction of Mycobacterium tuberculosis with DCs.

Open Access Article

Interactions of Salmonella enterica with dendritic cells

A. Leoni Swart and Michael Hensel
Pages 660 - 667
http://dx.doi.org/10.4161/viru.22761
Abstract | Full Text | PDF

Dendritic cells (DCs) form an important link between innate and adaptive immunity. However, DCs are also deployed as vehicles for systemic spread of pathogens. Salmonella is an important gastrointestinal pathogen causing diseases ranging from gastroenteritis to typhoid fever. DCs play an important role in the immunity against Salmonella infection, but this pathogen has also evolved efficient mechanisms to persist after phagocytosis by DCs, to spread using DCs as vehicles and to interfere with the central function of DCs, the processing of antigens and presentation of antigen-derived peptides to T cells for the stimulation of adaptive immune responses. Here we review the routes used by Salmonella to breach intestinal barriers, the intracellular habitat of Salmonella in DCs, molecular mechanisms of Salmonella virulence factors for intracellular life and intracellular activities in DCs resulting in manipulation of DC functions.

Open Access Article

How helminths use excretory secretory fractions to modulate dendritic cells

Rhiannon R. White and Katerina Artavanis-Tsakonas
Pages 668 - 677
http://dx.doi.org/10.4161/viru.22832
Abstract | Full Text | PDF

It is well known that helminth parasites have immunomodulatory effects on their hosts. They characteristically cause a skew toward T_H2 immunity, stimulate Treg cells while simultaneously inhibiting T_H1 and T_H17 responses. Additionally, they induce eosinophilia and extensive IgE release. The exact mechanism of how the worms achieve this effect have yet to be fully elucidated; however, parasite-derived secretions and their interaction with antigen presenting cells have been centrally implicated. Herein, we will review the effects of helminth excretory-secretory fractions on dendritic cells and discuss how this interaction is crucial in shaping the host response.

Open Access Article

Use and abuse of dendritic cells by Toxoplasma gondii

Anna Sanecka and Eva-Maria Frickel
Pages 678 - 689
http://dx.doi.org/10.4161/viru.22833
Abstract | Full Text | PDF

The ubiquitous apicomplexan parasite Toxoplasma gondii stimulates its host’s immune response to achieve quiescent chronic infection. Central to this goal are host dendritic cells. The parasite exploits dendritic cells to disseminate through the body, produce pro-inflammatory cytokines, present its antigens to the immune system and yet at the same time subvert their signaling pathways in order to evade detection. This carefully struck balance by Toxoplasma makes it the most successful parasite on this planet. Recent progress has highlighted specific parasite and host molecules that mediate some of these processes particularly in dendritic cells and in other cells of the innate immune system. Critically, there are several important factors that need to be taken into consideration when concluding how the dendritic cells and the immune system deal with a Toxoplasma infection, including the route of administration, parasite strain and host genotype.

Open Access Article

Insights into dendritic cell function using advanced imaging modalities

Jatin M. Vyas
Pages 690 - 694
http://dx.doi.org/10.4161/viru.22981
Abstract | Full Text | PDF

The application of advanced imaging techniques to fundamental questions in immunology has provided insight into dendritic cell function and has challenged dogma created using static imaging of lymphoid tissue. The history of dendritic cell biology has a storied past and is tightly linked to imaging. The development of imaging techniques that emphasize live cell imaging in situ has provided not only breath-taking movies, but also novel insights into the importance of spatiotemporal relationships between antigen presenting cells and T cells. This review serves to provide a primer on two-photon microscopy, TIRF microscopy, spinning disk confocal microscopy and optical trapping and provides selective examples of insights gained from these tools on dendritic cell biology.