Arturo Casadevall

Albert Einstein College of Medicine, New York, New York, United States

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Publications (645)3471.95 Total impact

  • Jacqueline M. Achkar, John Chan, Arturo Casadevall
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    ABSTRACT: Better understanding of the immunological components and their interactions necessary to prevent or control Mycobacterium tuberculosis (Mtb) infection in humans is critical for tuberculosis (TB) vaccine development strategies. Although the contributory role of humoral immunity in the protection against Mtb infection and disease is less defined than the role of T cells, it has been well-established for many other intracellular pathogens. Here we update and discuss the increasing evidence and the mechanisms of B cells and antibodies in the defense against Mtb infection. We posit that B cells and antibodies have a variety of potential protective roles at each stage of Mtb infection and postulate that such roles should be considered in the development strategies for TB vaccines and other immune-based interventions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    Immunological Reviews 03/2015; 264(1). · 12.91 Impact Factor
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    ABSTRACT: Human infection with Cryptococcus neoformans, a common fungal pathogen, follows deposition of yeast spores in the lung alveoli. The subsequent host-pathogen interaction can result in eradication, latency, or extrapulmonary dissemination. Successful control of C. neoformans infection is dependent on host macrophages, but macrophages display little ability to kill C. neoformans in vitro. Recently, we reported that ingestion of C. neoformans by mouse macrophages induces early cell cycle progression followed by mitotic arrest, an event that almost certainly reflects host cell damage. The goal of the present work was to understand macrophage pathways affected by C. neoformans toxicity. Infection of macrophages by C. neoformans was associated with alterations in protein translation rate and activation of several stress pathways, such as hypoxia-inducing factor-1-α, receptor-interacting protein 1, and apoptosis-inducing factor. Concomitantly we observed mitochondrial depolarization in infected macrophages, an observation that was replicated in vivo. We also observed differences in the stress pathways activated, depending on macrophage cell type, consistent with the nonspecific nature of C. neoformans virulence known to infect phylogenetically distant hosts. Our results indicate that C. neoformans infection impairs multiple host cellular functions and undermines the health of these critical phagocytic cells, which can potentially interfere with their ability to clear this fungal pathogen. Copyright © 2015 by The American Association of Immunologists, Inc.
    Journal of immunology (Baltimore, Md. : 1950). 02/2015;
  • Ferric C Fang, Arturo Casadevall
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    ABSTRACT: Science has always been a competitive undertaking. Despite recognition of the benefits of cooperation and team science, reduced availability of funding and jobs has made science more competitive than ever. Here we consider the benefits of competition in providing incentives to scientists and the adverse effects of competition on resource sharing, research integrity and creativity. The history of science shows that transformative discoveries often occur in the absence of competition, which only emerges once fields are established and goals are defined. Measures to encourage collaboration and ameliorate competition in the scientific enterprise are discussed. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Infection and immunity. 01/2015;
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    Arturo Casadevall, Jo Handelsman
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    ABSTRACT: ABSTRACT We investigated the hypothesis that the gender of conveners at scientific meetings influenced the gender distribution of invited speakers. Analysis of 460 symposia involving 1,845 speakers in two large meetings sponsored by the American Society for Microbiology revealed that having at least one woman member of the convening team correlated with a significantly higher proportion of invited female speakers and reduced the likelihood of an all-male symposium roster. Our results suggest that inclusion of more women as conveners may increase the proportion of women among invited speakers at scientific meetings. IMPORTANCE The proportion of women entering scientific careers has increased substantially, but women remain underrepresented in academic ranks. Participation in meetings as a speaker is a factor of great importance for academic advancement. We found that having a woman as a convener greatly increased women's participation in symposia, suggesting that one mechanism for achieving gender balance at scientific meetings is to involve more women as conveners.
    mBio 12/2014; 5(1). · 6.88 Impact Factor
  • Arturo Casadevall, Liise-anne Pirofski
    Nature 12/2014; 516(7530):165-6. · 42.35 Impact Factor
  • Arturo Casadevall, Liise-Anne Pirofski
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    ABSTRACT: Since proof of the germ theory of disease in the late 19(th) century a major focus of the fields of microbiology and infectious diseases has been to seek differences between pathogenic and non-pathogenic microbes and the role that the host plays in microbial pathogenesis. Remarkably, despite the increasing recognition that host immunity plays a role in microbial pathogenesis, there has been little discussion about what constitutes a host. Historically, hosts have been viewed in the context of their fitness or immunological status, and characterized by adjectives such as immune, immunocompetent, immunosuppressed, immunocompromised, or immunologically impaired. However, in recent years it has become apparent that the microbiota has profound effects on host homeostasis and susceptibility to microbial diseases in addition to its effects on host immunity. This raises the question of how to incorporate the microbiota into defining a host. This definitional problem is further complicated because neither host nor microbial properties are adequate to predict the outcome of host-microbe interaction because this outcome exhibits emergent properties. In this essay we revisit the 'damage-response framework' (DRF) of microbial pathogenesis and demonstrate how it can incorporate the rapidly accumulating information being generated by the microbiome revolution. We use the tenets of the DRF to put forth the following definition of a host: a host is an entity that houses an associated microbiome/microbiota and interacts with microbes such that the outcome results in damage, benefit, or indifference thus resulting in the states of symbiosis, colonization, commensalism, latency and disease.
    Infection and Immunity 11/2014; · 4.16 Impact Factor
  • Ekaterina Dadachova, Arturo Casadevall
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    ABSTRACT: Novel approaches to treatment of infectious diseases are urgently needed. This need has resulted in renewing the interest in antibodies for therapy of infectious diseases. Radioimmunotherapy (RIT) is a cancer treatment modality, which utilizes radiolabeled monoclonal antibodies (mAbs). During the last decade we have translated RIT into the field of experimental fungal, bacterial and HIV infections. In addition, successful proof of principle experiments with radiolabeled pan-antibodies that bind to antigens shared by major pathogenic fungi were performed in vitro. The armamentarium of pan-antibodies would result in reducing the dependence on microorganism-specific antibodies and thus would speed up the development of RIT of infections. We believe that the time is ripe for deploying RIT into the clinic to combat infectious diseases.
    Microbiology spectrum. 11/2014; 2(6):0023.
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    ABSTRACT: Review experimental evidence supporting the notion that the importance of humoral and cellular immunity in host defense may not be entirely determined by the niche of the pathogen (intracellular vs extracellular).•Provide evidence that antibodies contribute to the defense immune response against M. tuberculosis.•Discuss the how the multifacted B cells and humoral immunity can interact with T cells and other effector cells to shape the development of immune responses to M. tuberculosis.•Advocate for consideration a comprehensive approach that embraces both humoral and cellular immunity so as to gain better understanding of the immune response to M. tuberculosis.
    Seminars in Immunology 10/2014; · 5.93 Impact Factor
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    ABSTRACT: Regulatory T cells (Treg) play a critical role in the prevention of autoimmunity, and the suppressive activity of these cells is impaired in rheumatoid arthritis (RA). The aim of the present study was to investigate function and properties of Treg of RA patients in response to purified polysaccharide glucuronoxylomannogalactan (GXMGal).
    PLoS ONE 10/2014; 9(10):e111163. · 3.53 Impact Factor
  • Julie M. Wolf, Arturo Casadevall
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    ABSTRACT: Extracellular vesicles (EV) produced by eukaryotic microbes play an important role during infection. EV release is thought to benefit microbial invasion by delivering a high concentration of virulence factors to distal host cells or to the cytoplasm of a host cell. EV can significantly impact the outcome of host–pathogen interaction in a cargo-dependent manner. Release of EV from eukaryotic microbes poses unique challenges when compared to their bacterial or archaeal counterparts. Firstly, the membrane-bound organelles within eukaryotes facilitate multiple mechanisms of vesicle generation. Secondly, the fungal cell wall poses a unique barrier between the vesicle release site at the plasma membrane and its destined extracellular environment. This review focuses on these eukaryotic-specific aspects of vesicle synthesis and release.
    Current Opinion in Microbiology 10/2014; 22:73–78. · 7.22 Impact Factor
  • Jacqueline M Achkar, John Chan, Arturo Casadevall
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    ABSTRACT: Accumulating evidence has documented a role for B cells and antibodies (Abs) in the immunity against Mycobacterium tuberculosis (Mtb). Passive transfer studies with monoclonal antibodies (mAbs) against mycobacterial antigens have shown protection against the tubercle bacillus. B cells and Abs are believed to contribute to an enhanced immune response against Mtb by modulating various immunological components in the infected host including the T-cell compartment. Nevertheless, the extent and contribution of B cells and Abs to protection against Mtb remains uncertain. In this article we summarize the most relevant findings supporting the role of B cells and Abs in the defense against Mtb and discuss the potential mechanisms of protection.
    Cold Spring Harbor Perspectives in Medicine 10/2014; · 7.56 Impact Factor
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    ABSTRACT: The release of extracellular vesicles (EV) by fungal organisms is considered an alternative transport mechanism to trans-cell wall passage of macromolecules. Previous studies have revealed the presence of EV in culture supernatants from fungal pathogens, such as Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii, Malassezia sympodialis and Candida albicans. Here we investigated the size, composition, kinetics of internalization by bone-marrow derived murine macrophages (MO) and dendritic cells (DC), and the immunomodulatory activity of C. albicans EV. We also evaluated the impact of EVs on fungal virulence using the Galleria mellonella larvae model. By transmission electron microscopy and dynamic light scattering we identified two populations ranging from 50-100 and 350-850 nm. Two predominant seroreactive proteins (27 and 37 kDa) and a group of polydispersed mannoproteins were observed in EV by immunoblotting analysis. Proteomic analysis of C. albicans EV revealed proteins related to pathogenesis, cell organization, carbohydrate and lipid metabolism, response to stress and several other functions. The major lipids detected by thin layer chromatography were ergosterol, lanosterol and glucosylceramide. Short exposure of MO to EV resulted in internalization of these vesicles and production of nitric oxide, IL-12, TGF-β and IL-10. Similarly, EV-treated DC produced IL- 12p40, IL-10 and TNF-α. In addition, EV treatment induced the upregulation of CD86 and MHC-II. Inoculation of G. mellonella larvae with EV followed by challenge with C. albicans reduced the number of recovered viable yeasts in comparison to infected larvae control. Taking together, our results demonstrate that C. albicans EV were immunologically active and could potentially interfere with the host responses in the setting of invasive candidiasis.
    Cellular Microbiology 10/2014; · 4.82 Impact Factor
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    ABSTRACT: Pathogenic and nonpathogenic species of bacteria and fungi release membrane vesicles (MV), containing proteins, polysaccharides, and lipids, into the extracellular milieu. Previously, we demonstrated that several mycobacterial species, including bacillus Calmette-Guerin (BCG) and Mycobacterium tuberculosis, release MV containing lipids and proteins that subvert host immune response in a Toll-like receptor 2 (TLR2)-dependent manner (R. Prados-Rosales et al., J. Clin. Invest. 121:1471-1483, 2011, doi:10.1172/JCI44261). In this work, we analyzed the vaccine potential of MV in a mouse model and compared the effects of immunization with MV to those of standard BCG vaccination. Immunization with MV from BCG or M. tuberculosis elicited a mixed humoral and cellular response directed to both membrane and cell wall components, such as lipoproteins. However, only vaccination with M. tuberculosis MV was able to protect as well as live BCG immunization. M. tuberculosis MV boosted BCG vaccine efficacy. In summary, MV are highly immunogenic without adjuvants and elicit immune responses comparable to those achieved with BCG in protection against M. tuberculosis.
    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    Arturo Casadevall, Don Howard, Michael J Imperiale
    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    Arturo Casadevall, Don Howard, Michael J Imperiale
    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    Arturo Casadevall, Michael J Imperiale
    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    Arturo Casadevall, Don Howard, Michael J Imperiale
    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    Arturo Casadevall, Don Howard, Michael J Imperiale
    mBio 08/2014; 5(5). · 6.88 Impact Factor
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    ABSTRACT: The number of retracted scientific articles has been increasing. Most retractions are associated with research misconduct, entailing financial costs to funding sources and damage to the careers of those committing misconduct. We sought to calculate the magnitude of these effects. Data relating to retracted manuscripts and authors found by the Office of Research Integrity (ORI) to have committed misconduct were reviewed from public databases. Attributable costs of retracted manuscripts, and publication output and funding of researchers found to have committed misconduct were determined. We found that papers retracted due to misconduct accounted for approximately $58 million in direct funding by the NIH between 1992 and 2012, less than 1% of the NIH budget over this period. Each of these articles accounted for a mean of $392,582 in direct costs (SD $423,256). Researchers experienced a median 91.8% decrease in publication output and large declines in funding after censure by the ORI.DOI: http://dx.doi.org/10.7554/eLife.02956.001.
    eLife Sciences 08/2014; 3:e02956. · 8.52 Impact Factor

Publication Stats

20k Citations
3,471.95 Total Impact Points

Institutions

  • 1990–2015
    • Albert Einstein College of Medicine
      • • Department of Microbiology & Immunology
      • • Nuclear Medicine
      • • Infectious Diseases
      • • Department of Nuclear Medicine
      • • Department of Pediatrics
      • • Department of Medicine
      • • Department of Cell Biology
      New York, New York, United States
  • 2014
    • University of Notre Dame
      • Department of Philosophy
      South Bend, Indiana, United States
    • University of Michigan
      • Department of Microbiology and Immunology
      Ann Arbor, Michigan, United States
  • 2007–2014
    • Federal University of Rio de Janeiro
      • • Instituto de Biofísica Carlos Chagas Filho (IBCCF)
      • • Instituto de Microbiologia Professor Paulo de Góes (IMPPG)
      • • Instituto de Biologia (IB)
      Rio de Janeiro, Rio de Janeiro, Brazil
    • Trinity University of Asia
      Alfonso XIII, Mimaropa, Philippines
  • 2002–2014
    • Yeshiva University
      • • Albert Einstein College of Medicine
      • • Department of Microbiology & Immunology
      • • Division of Infectious Diseases
      • • Division of Hospital Medicine
      • • Division of Nuclear Medicine
      New York, New York, United States
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States
  • 2013
    • University of North Carolina at Chapel Hill
      North Carolina, United States
    • University of Brasília
      • Department of Cell Biology
      Brasília, Federal District, Brazil
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States
  • 2008–2013
    • University of Washington Seattle
      • Department of Medicine
      Seattle, WA, United States
    • Institute for Transuranium Elements
      Carlsruhe, Baden-Württemberg, Germany
    • Montefiore Medical Center
      • Department of Pediatrics
      New York City, NY, United States
    • Wayne State University
      • Department of Chemistry
      Detroit, Michigan, United States
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
    • City University of New York - Bronx Community College
      New York City, New York, United States
    • Farmingdale State College
      East Farmingdale, New York, United States
  • 2012
    • AECOM
      Sandy City, Utah, United States
    • University of Coimbra
      • Faculty of Medicine
      Coímbra, Coimbra, Portugal
    • Istituto Superiore di Sanità
      Roma, Latium, Italy
  • 2010–2012
    • The Commonwealth Medical College
      • Department of Basic Sciences
      Scranton, PA, United States
  • 2011
    • City University of New York - Bernard M. Baruch College
      • Department of Natural Sciences
      New York City, NY, United States
    • City University of New York - Brooklyn College
      • Department of Chemistry
      Brooklyn, New York, United States
    • CUNY Graduate Center
      New York City, New York, United States
  • 2009–2011
    • Instituto de Salud Carlos III
      • Center National of Microbiology (CNM)
      Madrid, Madrid, Spain
    • Centraalbureau voor Schimmelcultures
      Utrecht, Utrecht, Netherlands
  • 1998–2011
    • Università degli Studi di Perugia
      • Department of Clinical and Experimental Medicine
      Perugia, Umbria, Italy
    • University of Nevada School of Medicine
      Reno, Nevada, United States
  • 2006–2009
    • Department of Nuclear Medicine
      Nyitra, Nitriansky, Slovakia
  • 1993–2009
    • Stony Brook University
      • Department of Medicine
      Stony Brook, NY, United States
  • 2003–2008
    • City University of New York - College of Staten Island
      • Chemistry
      New York City, NY, United States
  • 1999–2008
    • Cornell University
      • • Department of Biological and Environmental Engineering
      • • Department of Pharmacology
      Ithaca, New York, United States
    • New York State
      New York City, New York, United States
  • 2005
    • Massachusetts General Hospital
      • Division of Infectious Diseases
      Boston, Massachusetts, United States
    • University of British Columbia - Vancouver
      • Biomedical Research Centre (BRC)
      Vancouver, British Columbia, Canada
    • Stockholm University
      • Department of Organic Chemistry
      Stockholm, Stockholm, Sweden
  • 2004
    • All India Institute of Medical Sciences
      • Department of Microbiology
      New Delhi, NCT, India
  • 2000–2003
    • Duke University Medical Center
      • • Division of Infectious Diseases
      • • Department of Medicine
      Durham, NC, United States
    • Università degli studi di Parma
      Parma, Emilia-Romagna, Italy
    • Venezuelan Institute for Scientific Research
      Caracas, Distrito Federal, Venezuela
  • 2001
    • The University of Manchester
      Manchester, England, United Kingdom
    • Long Island University
      • Department of Biology
      New York City, NY, United States
  • 1995–1999
    • Georgia State University
      • Department of Chemistry
      Atlanta, Georgia, United States
  • 1997
    • University of Oklahoma Health Sciences Center
      • Department of Microbiology and Immunology
      Oklahoma City, OK, United States