Stefan H E Kaufmann

Max Planck Institute for Infection Biology, Berlín, Berlin, Germany

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Publications (636)3562.29 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Tuberculosis continues to kill 1·4 million people annually. During the past 5 years, an alarming increase in the number of patients with multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis has been noted, particularly in eastern Europe, Asia, and southern Africa. Treatment outcomes with available treatment regimens for drug-resistant tuberculosis are poor. Although substantial progress in drug development for tuberculosis has been made, scientific progress towards development of interventions for prevention and improvement of drug treatment outcomes have lagged behind. Innovative interventions are therefore needed to combat the growing pandemic of multidrug-resistant and extensively drug-resistant tuberculosis. Novel adjunct treatments are needed to accomplish improved cure rates for multidrug-resistant and extensively drug-resistant tuberculosis. A novel, safe, widely applicable, and more effective vaccine against tuberculosis is also desperately sought to achieve disease control. The quest to develop a universally protective vaccine for tuberculosis continues. So far, research and development of tuberculosis vaccines has resulted in almost 20 candidates at different stages of the clinical trial pipeline. Host-directed therapies are now being developed to refocus the anti-Mycobacterium tuberculosis-directed immune responses towards the host; a strategy that could be especially beneficial for patients with multidrug-resistant tuberculosis or extensively drug-resistant tuberculosis. As we are running short of canonical tuberculosis drugs, more attention should be given to host-directed preventive and therapeutic intervention measures.
    The lancet. Respiratory medicine. 04/2014; 2(4):301-320.
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    ABSTRACT: Invariant NKT cells (iNKT cells) are innate lymphocytes that recognize lipid-derived Ags presented by the MHC class I-related protein CD1d. In this study, we analyzed the role of iNKT cells in the generation of Abs against HSV type 1 (HSV-1). In sera from healthy hman donors, we found a correlation between HSV-1-specific IgG titers and proportions of CD4(+) iNKT cells. In HSV-1-infected iNKT cell-deficient mice, the amount of specific IgM and IgG Abs were significantly reduced compared with wild-type mice. Moreover, iNKT cell-deficient mice were unable to upregulate CD1d on B cells and failed to establish an IFN-γ-driven subtype profile of HSV-1-specific IgG Abs. In spleens of HSV-1-infected wild-type mice, the percentage of iNKT cells expressing CCR6, a marker for inflammatory iNKT cells secreting IFN-γ, was significantly decreased at 6 mo postinfection, suggesting that these cells were released from the spleen to other tissues. Finally, in vitro experiments showed that in the absence of CD1d-restricted cells, HSV-1 induced markedly lower IFN-γ production in splenocytes from naive mice. Taken together, our results indicate that iNKT cells shape the Ab response to HSV-1 infection and provide a basis for rational development of antiviral vaccines.
    The Journal of Immunology 03/2014; · 5.52 Impact Factor
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    ABSTRACT: The emerging field of proteomics has contributed greatly to improving our understanding of the human pathogen Mycobacterium tuberculosis over the last two decades. In this chapter we provide a comprehensive overview of mycobacterial proteome research and highlight key findings. First, studies employing a combination of two-dimensional gel electropho-resis and mass spectrometry (MS) provided insights into the proteomic composition, initially of the whole bacillus and sub-sequently of subfractions, such as the cell wall, cytosol, and secreted proteins. Comparison of results obtained under various culture conditions, i.e., acidic pH, nutrient starvation, and low oxygen tension, aiming to mimic facets of the intracellular life-style of M. tuberculosis, provided initial clues to proteins relevant for intracellular survival and manipulation of the host cell. Fur-ther attempts were aimed at identifying the biological functions of the hypothetical M. tuberculosis proteins, which still make up a quarter of the gene products of M. tuberculosis, and at char-acterizing posttranslational modifications. Recent technological advances in MS have given rise to new methods such as selected reaction monitoring (SRM) and data-independent acquisition (DIA). These targeted, cutting-edge techniques combined with a public database of specific MS assays covering the entire proteome of M. tuberculosis allow the simple and reliable de-tection of any mycobacterial protein. Most recent studies at-tempt not only to identify but also to quantify absolute amounts of single proteins in the complex background of host cells without prior sample fractionation or enrichment. Finally, we will discuss the potential of proteomics to advance vaccinology, drug discovery, and biomarker identification to improve inter-vention and prevention measures for tuberculosis. More than 60 years ago, Swedish biochemist Pehr Edman introduced the first technique for single peptide
    Microbiology Spectrum. 03/2014; 2(2).
  • Francesca Chiodi, Stefan H. E. Kaufmann
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    ABSTRACT: Recent developments in the field of vaccination against human immunodeficiency virus (HIV) tuberculosis (TB) and malaria were recently reviewed during a course organized in October 2013 by the Ruggero Ceppellini Advanced School of Immunology under the sponsorship of the European Federation of Immunological Societies, the Bill and Melinda Gates Foundation and the Journal of Internal Medicine. During the course entitled ‘Novel vaccination strategies against the three major killers’, the latest advances in the field of vaccines against HIV, TB and malaria as well as vaccine development in general were presented. Expert scientists working on different aspects of vaccination against these three pathogens and related diseases gathered for this course.This article is protected by copyright. All rights reserved.
    Journal of Internal Medicine 03/2014; · 6.46 Impact Factor
  • January Weiner, Stefan H. E. Kaufmann
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    ABSTRACT: Of all infectious diseases, tuberculosis (TB) remains one of the most important causes of morbidity and mortality. Recent advances in understanding the biology of Mycobacterium tuberculosis (Mtb) infection and the immune response of the infected host have led to the development of several new vaccines, a number of which are already undergoing clinical trials. These include pre-exposure prime vaccines, which could replace bacille Calmette–Guérin (BCG), and pre-exposure booster vaccines given in addition to BCG. Infants are the target population of these two types of vaccines. In addition, several post-exposure vaccines given during adolescence or adult life, in addition to BCG as a priming vaccine during infancy, are undergoing clinical testing. Therapeutic vaccines are currently being assessed for their potential to cure active TB as an adjunct to chemotherapy. BCG-replacement vaccines are viable recombinant BCG or double-deletion mutants of Mtb. All booster vaccines are composed of one or several antigens, either expressed by viral vectors or formulated with adjuvants. Therapeutic vaccines are killed mycobacterial preparations. Finally, multivariate biomarkers and biosignatures are being generated from high-throughput data with the aim of providing better diagnostic tools to specifically determine TB progression. Here we provide a technical overview of these recent developments as well of the relevant computational approaches, and highlight the obstacles that still need to be overcomeThis article is protected by copyright. All rights reserved.
    Journal of Internal Medicine 03/2014; · 6.46 Impact Factor
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    ABSTRACT: B lymphocytes have critical roles as positive and negative regulators of immunity. Their inhibitory function has been associated primarily with interleukin 10 (IL-10) because B-cell-derived IL-10 can protect against autoimmune disease and increase susceptibility to pathogens. Here we identify IL-35-producing B cells as key players in the negative regulation of immunity. Mice in which only B cells did not express IL-35 lost their ability to recover from the T-cell-mediated demyelinating autoimmune disease experimental autoimmune encephalomyelitis (EAE). In contrast, these mice displayed a markedly improved resistance to infection with the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium as shown by their superior containment of the bacterial growth and their prolonged survival after primary infection, and upon secondary challenge, compared to control mice. The increased immunity found in mice lacking IL-35 production by B cells was associated with a higher activation of macrophages and inflammatory T cells, as well as an increased function of B cells as antigen-presenting cells (APCs). During Salmonella infection, IL-35- and IL-10-producing B cells corresponded to two largely distinct sets of surface-IgM(+)CD138(hi)TACI(+)CXCR4(+)CD1d(int)Tim1(int) plasma cells expressing the transcription factor Blimp1 (also known as Prdm1). During EAE, CD138(+) plasma cells were also the main source of B-cell-derived IL-35 and IL-10. Collectively, our data show the importance of IL-35-producing B cells in regulation of immunity and highlight IL-35 production by B cells as a potential therapeutic target for autoimmune and infectious diseases. This study reveals the central role of activated B cells, particularly plasma cells, and their production of cytokines in the regulation of immune responses in health and disease.
    Nature 02/2014; · 38.60 Impact Factor
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    ABSTRACT: The intestinal microbiota influences not only metabolic processes, but also the mucosal and systemic immune systems. Here, we compare innate and adaptive immune responses against the intracellular pathogen Listeria monocytogenes in germfree (GF) and conventional mice. We show that animals without endogenous microbiota are highly susceptible to primary infection with impaired activation and accumulation of phagocytes to the site of infection. Unexpectedly, secondary infection with otherwise lethal dose resulted in survival of all GF animals which cleared bacteria more rapidly and developed a stronger anti-listerial CD8(+) memory T-cell response compared to conventional mice. In summary, lack of the intestinal microbiota impairs early innate immunity, but enhances activation and expansion of memory T cells. This article is protected by copyright. All rights reserved.
    European Journal of Immunology 02/2014; · 4.97 Impact Factor
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    ABSTRACT: Successful host defense against numerous pulmonary infections depends on bacterial clearance by polymorphonuclear leukocytes (PMNs); however, excessive PMN accumulation can result in life-threatening lung injury. Local expression of CXC chemokines is critical for PMN recruitment. The impact of chemokine-dependent PMN recruitment during pulmonary Mycobacterium tuberculosis infection is not fully understood. Here, we analyzed expression of genes encoding CXC chemokines in M. tuberculosis-infected murine lung tissue and found that M. tuberculosis infection promotes upregulation of Cxcr2 and its ligand Cxcl5. To determine the contribution of CXCL5 in pulmonary PMN recruitment, we generated Cxcl5-/- mice and analyzed their immune response against M. tuberculosis. Both Cxcr2-/- mice and Cxcl5-/- mice, which are deficient for only one of numerous CXCR2 ligands, exhibited enhanced survival compared with that of WT mice following high-dose M. tuberculosis infection. The resistance of Cxcl5-/- mice to M. tuberculosis infection was not due to heightened M. tuberculosis clearance but was the result of impaired PMN recruitment, which reduced pulmonary inflammation. Lung epithelial cells were the main source of CXCL5 upon M. tuberculosis infection, and secretion of CXCL5 was reduced by blocking TLR2 signaling. Together, our data indicate that TLR2-induced epithelial-derived CXCL5 is critical for PMN-driven destructive inflammation in pulmonary tuberculosis.
    The Journal of clinical investigation 02/2014; · 15.39 Impact Factor
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    ABSTRACT: Cytokine induction in response toMycobacterium tuberculosis(Mtb) infection is critical for pathogen control, by (i) mediating innate immune effector functions and (ii)instructing specific adaptive immunity. IL-10 is an important anti-inflammatory cytokine involved in pathogenesis of tuberculosis (TB). Here, we show that TLR3, a sensor of extracellular viral or host RNA with stable stem structures derived from infected or damaged cells, is essential for Mtb-induced IL-10 production. Upon M. bovis Bacillus Calmette-Guérin (BCG) infection, TLR3(-/-) macrophages expressed lower IL-10 but higher IL12p40 production, accompanied by reducedphosphorylation of AKT at Ser473. BCG-infected TLR3(-/-)mice exhibited reduced IL-10 but elevated IL-12expression compared to controls. Moreover, higher numbers of splenic Th1 cells andreduced pulmonary bacterial burden and tissue damage were observed in BCG-infected TLR3(-/-) mice. Finally, BCG RNA induced IL-10 in macrophages via TLR3-mediated activation of PI3K/AKT. Our findings demonstrate a critical role of TLR3-mediated regulation in the pathogenesis of mycobacterial infectioninvolving mycobacterialRNA,which induces IL-10 through the PI3K/AKT signaling pathway.
    Cellular signalling 01/2014; · 4.09 Impact Factor
  • Eur J Immunol. 01/2014; 44(1):80-92.
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    ABSTRACT: Tuberculosis (TB) is a major health issue globally. Although typically the disease can be cured by chemotherapy in all age groups, and prevented in part in newborn by vaccination, general consensus exists that development of novel intervention measures requires better understanding of disease mechanisms. Human TB is characterized by polarity between host resistance as seen in 2 billion individuals with latent TB infection and susceptibility occurring in 9 million individuals who develop active TB disease every year. Experimental animal models often do not reflect this polarity adequately, calling for a reverse translational approach. Gene expression profiling has allowed identification of biomarkers that discriminate between latent infection and active disease. Functional analysis of most relevant markers in experimental animal models can help to better understand mechanisms driving disease progression. We have embarked on in-depth characterization of candidate markers of pathology and protection hereby harnessing mouse mutants with defined gene deficiencies. Analysis of mutants deficient in miR-223 expression and CXCL5 production allowed elucidation of relevant pathogenic mechanisms. Intriguingly, these deficiencies were linked to aberrant neutrophil activities. Our findings point to a detrimental potential of neutrophils in TB. Reciprocally, measures that control neutrophils should be leveraged for amelioration of TB in adjunct to chemotherapy.
    Frontiers in Immunology 01/2014; 5:36.
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    ABSTRACT: To date, little is known about the unique contributions of specialized human DC subsets to protection against tuberculosis (TB). Here, we focus on the role of human plasmacytoid (p)DCs and myeloid (m)DCs in the immune response to the TB vaccine bacille Calmette-Gu ́erin (BCG). Ex vivo DC subsets from human peripheral blood were purified and infected with BCG expressing GFP to distinguish between infected and noninfected cells. BDCA-1+ myeloid DCs were more susceptible than BDCA-3+ mDCs to BCG infection. Plasmacytoid DCs have poor phagocytic activity but are equipped with endocytic receptors and can be activated by bystander stimulation. Consequently, the mutual interaction of the two DC subsets in response to BCG was analyzed. We found that pDCs were activated by BCG-infected BDCA-1+ mDCs to upregulate maturation markers and to produce granzyme B, but not IFN-α. Reciprocally, the presence of activated pDCs enhanced mycobacterial growth control by infected mDCs and increased IL-1β availability. The synergy between the two DC subsets promoted BCG-specific CD8+ T-cell stimulation and the role of BCG-infected BDCA-1+ mDCs could not be efficiently replaced by infected BDCA-3+ mDCs in the crosstalk with pDCs. We conclude that mDC–pDC crosstalk should be exploited for rational design of next-generation TB vaccines.
    European Journal of Immunology 01/2014; 44(1):80-92. · 4.97 Impact Factor
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    ABSTRACT: New diagnostics and vaccines for tuberculosis (TB) are urgently needed, but require an understanding of the requirements for protection from/susceptibility to TB. Previous studies have used unbiased approaches to determine gene signatures in single-site populations. The present study utilized a targeted approach, reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA), to validate these genes in a multisite study. We analysed ex vivo whole blood RNA from a total of 523 participants across four sub-Saharan countries (Ethiopia, Malawi, South Africa, and The Gambia) with differences in TB and human immunodeficiency virus (HIV) status. We found a number of genes that were expressed at significantly lower levels in participants with active disease than in those with latent TB infection (LTBI), with restoration following successful TB treatment. The most consistent classifier of active disease was FCGR1A (high-affinity IgG Fc receptor 1 (CD64)), which was the only marker expressed at significantly higher levels in participants with active TB than in those with LTBI before treatment regardless of HIV status or genetic background. This is the first study to identify a biomarker for TB that is not affected by HIV status or geo-genetic differences. These data provide valuable clues for understanding TB pathogenesis, and also provide a proof-of-concept for the use of RT-MLPA in rapid and inexpensive validation of unbiased gene expression findings.
    Clinical Microbiology and Infection 12/2013; · 4.58 Impact Factor
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    ABSTRACT: Bacillus Calmette-Guérin (BCG), the only approved tuberculosis vaccine, provides only limited protection. Previously, we generated a recombinant derivative (BCG ΔureC::hly), which secretes the pore-forming toxin listeriolysin O (LLO) of Listeria monocytogenes. This vaccine shows superior protection against tuberculosis in preclinical models and is safe in humans. Here we describe two new vaccine strains which express human interleukin-7 (hIL)-7 or hIL-18 in the genetic background of BCG ΔureC::hly to modulate specific T cell immunity. Both strains exhibited an uncompromised in vitro growth pattern, while inducing a proinflammatory cytokine profile in human dendritic cells (DCs). Human DCs harbouring either strain efficiently promoted secretion of IL-2 by autologous T cells in a coculture system, suggesting superior immunogenicity. BALB/c mice vaccinated with BCG ΔureC::hly, BCG ΔureC::hly_hIL7 or BCG ΔureC::hly_hIL18 developed a more robust Th1 response than after vaccination with parental BCG. Both strains provided significantly better protection than BCG in a murine Mycobacterium tuberculosis challenge model but efficacy remained comparable to that afforded by BCG ΔureC::hly. We conclude that expression of hIL-7 or hIL-18 enhanced specific T cell responses but failed to improve protection over BCG ΔureC::hly in mice.
    PLoS ONE 11/2013; 8(11):e78966. · 3.73 Impact Factor
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    Ulrike Jung, Xiaoou Jiang, Stefan H E Kaufmann, Volker Patzel
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    ABSTRACT: Several methods for the detection of RNA have been developed over time. For small RNA detection, a stem-loop reverse primer-based protocol relying on TaqMan RT-PCR has been described. This protocol requires an individual specific TaqMan probe for each target RNA and, hence, is highly cost-intensive for experiments with small sample sizes or large numbers of different samples. We describe a universal TaqMan-based probe protocol which can be used to detect any target sequence and demonstrate its applicability for the detection of endogenous as well as artificial eukaryotic and bacterial small RNAs. While the specific and the universal probe-based protocol showed the same sensitivity, the absolute sensitivity of detection was found to be more than 100-fold lower for both than previously reported. In subsequent experiments, we found previously unknown limitations intrinsic to the method affecting its feasibility in determination of mature template RISC incorporation as well as in multiplexing. Both protocols were equally specific in discriminating between correct and incorrect small RNA targets or between mature miRNA and its unprocessed RNA precursor, indicating the stem-loop RT-primer, but not the TaqMan probe, triggers target specificity. The presented universal TaqMan-based RT-PCR protocol represents a cost-efficient method for the detection of small RNAs.
    RNA 10/2013; · 5.09 Impact Factor
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    ABSTRACT: The molecular mechanisms that control innate immune cell trafficking during chronic infection and inflammation, such as in tuberculosis (TB), are incompletely understood. During active TB, myeloid cells infiltrate the lung and sustain local inflammation. While the chemoattractants that orchestrate these processes are increasingly recognized, the posttranscriptional events that dictate their availability are unclear. We identified microRNA-223 (miR-223) as an upregulated small noncoding RNA in blood and lung parenchyma of TB patients and during murine TB. Deletion of miR-223 rendered TB-resistant mice highly susceptible to acute lung infection. The lethality of miR-223-/- mice was apparently not due to defects in antimycobacterial T cell responses. Exacerbated TB in miR-223-/- animals could be partially reversed by neutralization of CXCL2, CCL3, and IL-6, by mAb depletion of neutrophils, and by genetic deletion of Cxcr2. We found that miR-223 controlled lung recruitment of myeloid cells, and consequently, neutrophil-driven lethal inflammation. We conclude that miR-223 directly targets the chemoattractants CXCL2, CCL3, and IL-6 in myeloid cells. Our study not only reveals an essential role for a single miRNA in TB, it also identifies new targets for, and assigns biological functions to, miR-223. By regulating leukocyte chemotaxis via chemoattractants, miR-223 is critical for the control of TB and potentially other chronic inflammatory diseases.
    The Journal of clinical investigation 10/2013; · 15.39 Impact Factor
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    ABSTRACT: To date, little is known about the unique contributions of specialized human DC subsets to protection against tuberculosis (TB). Here, we focus on the role of human plasmacytoid (p)DCs and myeloid (m)DCs in the immune response to the TB vaccine bacille Calmette-Guérin (BCG). Ex vivo DC subsets from human peripheral blood were purified and infected with BCG expressing GFP to distinguish between infected and non-infected cells. BDCA-1(+) mDCs were more susceptible than BDCA-3(+) mDCs to BCG infection. pDCs have poor phagocytic activity but are equipped with endocytic receptors and can be activated by bystander stimulation. Consequently, the mutual interaction of the two DC subsets in response to BCG was analyzed. We found that pDCs were activated by BCG-infected BDCA-1(+) mDCs to upregulate maturation markers and to produce granzyme B, but not IFN-α. Reciprocally, the presence of activated pDCs enhanced mycobacterial growth control by infected mDCs and increased IL-1β availability. The synergy between the two DC subsets promoted BCG-specific CD8(+) T-cell stimulation and the role of BCG-infected BDCA-1(+) mDCs could not be efficiently replaced by infected BDCA-3(+) mDCs in the crosstalk with pDCs. We conclude that mDC-pDC crosstalk should be exploited for rational design of next-generation TB vaccines. This article is protected by copyright. All rights reserved.
    European Journal of Immunology 09/2013; · 4.97 Impact Factor
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    S H Kaufmann, J Hess
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    ABSTRACT: BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. METHODS: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. RESULTS: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials
    PLoS ONE 09/2013; 8(9):e74080. · 3.73 Impact Factor

Publication Stats

18k Citations
3,562.29 Total Impact Points

Institutions

  • 1996–2014
    • Max Planck Institute for Infection Biology
      • Department of Immunology
      Berlín, Berlin, Germany
  • 2012
    • Biomedical primate research centre
      • Parasitology
      Rijswijk, South Holland, Netherlands
    • French National Centre for Scientific Research
      • Institute of Pharmacology and Structural Biology
      Lutetia Parisorum, Île-de-France, France
    • Sokoine University of Agriculture (SUA)
      Murogoro, Morogoro Region, Tanzania
    • Leiden University Medical Centre
      • Department of Infectious Diseases
      Leiden, South Holland, Netherlands
  • 2011
    • Bernhard Nocht Institute for Tropical Medicine
      Hamburg, Hamburg, Germany
  • 1991–2011
    • Technische Universität München
      • Institut für Medizinische Mikrobiologie, Immunologie und Hygiene
      München, Bavaria, Germany
  • 2010
    • Stellenbosch University
      • Department of Paediatrics and Child Health
      Stellenbosch, Province of the Western Cape, South Africa
    • Yale University
      • Department of Immunobiology
      New Haven, CT, United States
    • Leibniz Institute for Farm Animal Biology
      Dummerstorf, Mecklenburg-Vorpommern, Germany
    • Research Center Borstel
      Borstel, Lower Saxony, Germany
  • 2007–2010
    • London School of Hygiene and Tropical Medicine
      • Department of Immunology and Infection
      Londinium, England, United Kingdom
    • University of Greifswald
      • Institute for Microbiology
      Greifswald, Mecklenburg-Vorpommern, Germany
    • Vanderbilt University
      Nashville, Michigan, United States
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 2009
    • University of Oxford
      • Jenner Institute
      Oxford, ENG, United Kingdom
    • Makerere University
      • School of Medicine
      Kampala, Central Region, Uganda
  • 2003–2008
    • Charité Universitätsmedizin Berlin
      • • Institute of Virology
      • • Department of Pediatrics, Division of Pneumonology and Immunology
      • • Institute of Biochemistry
      Berlin, Land Berlin, Germany
  • 1990–2008
    • Universität Heidelberg
      • Institute of Immunology and Serology
      Heidelburg, Baden-Württemberg, Germany
  • 2006
    • European Federation of Immunological Societies
      Berlín, Berlin, Germany
    • Howard Hughes Medical Institute
      Maryland, United States
    • European Molecular Biology Laboratory
      Heidelburg, Baden-Württemberg, Germany
    • National Institute of Infectious Diseases, Tokyo
      Edo, Tōkyō, Japan
  • 2002–2006
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
    • Max Planck Institute for Empirical Aesthetics
      Frankfurt, Hesse, Germany
  • 2004
    • Statens Serum Institut
      • Department of Infectious Disease Immunology
      København, Capital Region, Denmark
  • 1988–2002
    • Universität Ulm
      • • Institute of Microbiology and Biotechnology
      • • Institute of Medical Microbiology and Hygiene
      Ulm, Baden-Wuerttemberg, Germany
    • Max Planck Institute of Immunobiology and Epigenetics
      Freiburg, Baden-Württemberg, Germany
  • 1997–2001
    • University of Wuerzburg
      • Department of Microbiology
      Würzburg, Bavaria, Germany
  • 2000
    • University of Leipzig
      Leipzig, Saxony, Germany
  • 1999
    • Fundação de Dermatologia Tropical e Venereologia Alfredo da Matta
      Cachoeirinha, Pernambuco, Brazil
  • 1989
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 1982–1983
    • Freie Universität Berlin
      Berlín, Berlin, Germany