Arturo Casadevall

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

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Publications (650)3494.66 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In recent years several groups have shown that isotype switching from IgM to IgG to IgA can affect the affinity and specificity of antibodies (Abs) sharing identical variable (V) regions. However, whether the same applies to IgE is unknown. In this study we compared the fine specificity of V region identical IgE and IgA to Cryptococcus neoformans capsular polysaccharide and found that these differed in specificity from each other. The IgE and IgA paratopes were probed by nuclear magnetic resonance spectroscopy (NMR) with 15Nlabeled peptide mimetics of cryptococcal polysaccharide antigen (Ag). IgE was found to cleave the peptide at a much faster rate than V region-identical IgG subclasses and IgA, consistent with an altered paratope. Both IgE and IgA were opsonic for C. neoformans and protected against infection in mice. In summary, V region expression in the context of the epsilon constant (C) region results in specificity changes that are greater than observed for comparable IgG subclasses. These results raise the possibility that expression of certain V regions in the context of alpha and epsilon C regions affects their function and contributes to the special properties of those isotypes. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
  • 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). DOI:10.1111/imr.12276 · 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.
  • 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.
  • Michael J Imperiale, Arturo Casadevall
    mBio 01/2015; 6(2). DOI:10.1128/mBio.00236-15 · 6.88 Impact Factor
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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). DOI:10.1128/mBio.00846-13 · 6.88 Impact Factor
  • Arturo Casadevall, Liise-anne Pirofski
    Nature 12/2014; 516(7530):165-6. DOI:10.1038/516165a · 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; 83(1). DOI:10.1128/IAI.02627-14 · 4.16 Impact Factor
  • Julia R Köhler, Arturo Casadevall, John Perfect
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    ABSTRACT: Few among the millions of fungal species fulfill four basic conditions necessary to infect humans: high temperature tolerance, ability to invade the human host, lysis and absorption of human tissue, and resistance to the human immune system. In previously healthy individuals, invasive fungal disease is rare because animals' sophisticated immune systems evolved in constant response to fungal challenges. In contrast, fungal diseases occur frequently in immunocompromised patients. Paradoxically, successes of modern medicine have put increasing numbers of patients at risk for invasive fungal infections. Uncontrolled HIV infection additionally makes millions vulnerable to lethal fungal diseases. A concerted scientific and social effort is needed to meet these challenges.
    Cold Spring Harbor Perspectives in Medicine 11/2014; 5(1). DOI:10.1101/cshperspect.a019273 · 7.56 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.
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    Arturo Casadevall, Thomas Shenk
    mBio 10/2014; 5(6). DOI:10.1128/mBio.02434-14 · 6.88 Impact Factor
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    Michael J Imperiale, Arturo Casadevall
    mBio 10/2014; 5(6). DOI:10.1128/mBio.02292-14 · 6.88 Impact Factor
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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; 26(6). DOI:10.1016/j.smim.2014.10.005 · 5.93 Impact Factor
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    ABSTRACT: Objective: 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). Methods: Flow cytometry and western blot analysis were used to investigate the frequency, function and properties of Treg cells. Results: GXMGal was able to: i) induce strong increase of FOXP3 on CD4(+) T cells without affecting the number of CD4(+)CD25(+)FOXP3(+) Treg cells with parallel increase in the percentage of non-conventional CD4(+)CD25(-)FOXP3(+) Treg cells; ii) increase intracellular levels of TGF-beta 1 in CD4(+)CD25(-)FOXP3(+) Treg cells and of IL-10 in both CD4(+)CD25(+)FOXP3(+) and CD4(+)CD25(-)FOXP3(+) Treg cells; iii) enhance the suppressive activity of CD4(+)CD25(+)FOXP3(+) and CD4(+)CD25(-)FOXP3(+) Treg cells in terms of inhibition of effector T cell activity and increased secretion of IL-10; iv) decrease Th1 response as demonstrated by inhibition of T-bet activation and down-regulation of IFN-gamma and IL-12p70 production; v) decrease Th17 differentiation by down-regulating pSTAT3 activation and IL-17A, IL-23, IL-21, IL-22 and IL-6 production. Conclusion: These data show that GXMGal improves Treg functions and increases the number and function of CD4(+)CD25(-)FOXP3(+) Treg cells of RA patients. It is suggested that GXMGal may be potentially useful for restoring impaired Treg functions in autoimmune disorders and for developing Treg cell-based strategies for the treatment of these diseases.
    PLoS ONE 10/2014; 9(10):e111163. DOI:10.1371/journal.pone.0111163 · 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. DOI:10.1016/j.mib.2014.09.012 · 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; DOI:10.1101/cshperspect.a018432 · 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; DOI:10.1111/cmi.12374 · 4.82 Impact Factor
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    Arturo Casadevall, Don Howard, Michael J Imperiale
    mBio 08/2014; 5(5). DOI:10.1128/mBio.01875-14 · 6.88 Impact Factor
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    Arturo Casadevall, Michael J Imperiale
    mBio 08/2014; 5(5). DOI:10.1128/mBio.01860-14 · 6.88 Impact Factor
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    Arturo Casadevall, Don Howard, Michael J Imperiale
    mBio 08/2014; 5(5). DOI:10.1128/mBio.02053-14 · 6.88 Impact Factor

Publication Stats

21k Citations
3,494.66 Total Impact Points

Institutions

  • 1990–2015
    • Albert Einstein College of Medicine
      • • Department of Microbiology & Immunology
      • • Department of Pediatrics
      • • Infectious Diseases
      • • Department of Nuclear Medicine
      • • 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
  • 2007–2014
    • Federal University of Rio de Janeiro
      • • Instituto de Biofísica Carlos Chagas Filho (IBCCF)
      • • Institute of Biomedical Sciences
      • • 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
  • 2006–2014
    • Yeshiva University
      • • Albert Einstein College of Medicine
      • • Department of Microbiology & Immunology
      • • Division of Infectious Diseases
      • • Department of Medicine
      • • Division of Nuclear Medicine
      New York, New York, United States
    • Institute for Transuranium Elements
      Carlsruhe, Baden-Württemberg, Germany
  • 2012
    • University of Coimbra
      • Faculty of Medicine
      Coímbra, Coimbra, Portugal
    • Istituto Superiore di Sanità
      Roma, Latium, Italy
    • AECOM
      Sandy, Utah, United States
  • 2008–2012
    • University of Washington Seattle
      Seattle, Washington, United States
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
    • Wayne State University
      • Department of Chemistry
      Detroit, Michigan, United States
    • City University of New York - Bronx Community College
      New York City, New York, United States
  • 2011
    • City University of New York - Bernard M. Baruch College
      • Department of Natural Sciences
      New York City, NY, United States
  • 2010
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • The Commonwealth Medical College
      • Department of Basic Sciences
      Scranton, PA, United States
  • 2009
    • Stony Brook University
      • Department of Medicine
      Stony Brook, NY, United States
  • 2004–2008
    • Cornell University
      • Department of Biological and Environmental Engineering
      Ithaca, New York, United States
    • All India Institute of Medical Sciences
      • Department of Microbiology
      New Delhi, NCT, India
  • 2006–2007
    • Department of Nuclear Medicine
      Nyitra, Nitriansky, Slovakia
  • 2005
    • Massachusetts General Hospital
      • Division of Infectious Diseases
      Boston, Massachusetts, United States
    • Worcester Polytechnic Institute
      • Department of Chemical Engineering
      Worcester, Massachusetts, United States
  • 2000–2003
    • Duke University Medical Center
      • • Department of Molecular Genetics and Microbiology
      • • Division of Infectious Diseases
      Durham, NC, United States
    • Venezuelan Institute for Scientific Research
      Caracas, Distrito Federal, Venezuela
    • Università degli studi di Parma
      Parma, Emilia-Romagna, Italy
  • 2001
    • The University of Manchester
      Manchester, England, United Kingdom
    • Long Island University
      • Department of Biology
      New York City, NY, United States
  • 1999
    • New York State
      New York City, New York, United States
  • 1995–1999
    • Georgia State University
      • Department of Chemistry
      Atlanta, Georgia, United States
  • 1998
    • University of Nevada School of Medicine
      Reno, Nevada, United States