Stefan H E Kaufmann

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

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Publications (665)3706.45 Total impact

  • Anca Dorhoi, Stefan H.E. Kaufmann
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    ABSTRACT: Pro- and anti-inflammatory mechanisms contribute equally to establishment and progression of tuberculosis.•Inflammatory mediators exhibit distinct roles at various stages of tuberculosis. Therefore in-depth temporal characterization of inflammation can provide guidelines for future interventions.•Inflammatory events are conditioned by distinct inflammatory microenvironments and depend on lung anatomy and physiological imprints.•Granuloma caseation, tissue liquefaction and lung cavitation form the basis for disease transmission.
    Seminars in Immunology 10/2014; · 5.93 Impact Factor
  • Jeroen Maertzdorf, Stefan H E Kaufmann, January Weiner
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    ABSTRACT: Accurate and rapid diagnosis of active tuberculosis (TB) disease is still hampered by inadequate tools. Although current assays relying on single-marker readouts mostly display inadequate sensitivity and/or specificity, host-related multimarker signatures are especially poorly developed. As a consequence, research programs have been initiated to search for combinations of markers-so-called biosignatures with superior performance. Many such investigations harness high-throughput platforms to analyze the host response during infection and disease. A major challenge for these activities is the analysis of vast amounts of data produced. Specialized bioinformatic tools are being applied to identify the most robust biosignatures for classification of exposed and diseased individuals and prognosis of risk of disease in endemic areas. Validation of the most promising biosignatures in ongoing multicohort studies will bring us a step closer to the identification of an accurate unified signature.
    Cold Spring Harbor perspectives in medicine. 10/2014;
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    ABSTRACT: Tuberculosis (TB) diagnosis in low-income countries is mainly done by microscopy. Hence, little is known about the diversity of Mycobacterium spp. in TB infections. Different genotypes or lineages of Mycobacterium tuberculosis vary in virulence and induce different inflammatory and immune responses. Trained Cricetomys rats show a potential for rapid diagnosis of TB. They detect over 28 % of smear-negative, culture-positive TB. However, it is unknown whether these rats can equally detect sputa from patients infected with different genotypes of M. tuberculosis. A 4-month prospective study on diversity of Mycobacterium spp. was conducted in Dar es Salaam, Tanzania. 252 sputa from 161 subjects were cultured on Lowenstein-Jensen medium and thereafter tested by rats. Mycobacterial isolates were subjected to molecular identification and multispacer sequence typing (MST) to determine species and genotypes. A total of 34 Mycobacterium spp. isolates consisting of 32 M. tuberculosis, 1 M. avium subsp. hominissuis and 1 M. intracellulare were obtained. MST analyses of 26 M. tuberculosis isolates yielded 10 distinct MST genotypes, including 3 new genotypes with two clusters of related patterns not grouped by geographic areas. Genotype MST-67, shared by one-third of M. tuberculosis isolates, was associated with the Mwananyamala clinic. This study shows that diverse M. tuberculosis genotypes (n = 10) occur in Dar es Salaam and trained rats detect 80 % of the genotypes. Sputa with two M. tuberculosis genotypes (20 %), M. avium hominissuis and M. intracellulare were not detected. Therefore, rats detect sputa with different M. tuberculosis genotypes and can be used to detect TB in resource-poor countries.
    Current microbiology. 10/2014;
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    ABSTRACT: Lung granulomas develop upon Mycobacterium tuberculosis (Mtb) infection as a hallmark of human tuberculosis (TB). They are structured aggregates consisting mainly of Mtb-infected and -uninfected macrophages and Mtb-specific T cells. The production of NO by granuloma macrophages expressing nitric oxide synthase-2 (NOS2) via l-arginine and oxygen is a key protective mechanism against mycobacteria. Despite this protection, TB granulomas are often hypoxic, and bacterial killing via NOS2 in these conditions is likely suboptimal. Arginase-1 (Arg1) also metabolizes l-arginine but does not require oxygen as a substrate and has been shown to regulate NOS2 via substrate competition. However, in other infectious diseases in which granulomas occur, such as leishmaniasis and schistosomiasis, Arg1 plays additional roles such as T-cell regulation and tissue repair that are independent of NOS2 suppression. To address whether Arg1 could perform similar functions in hypoxic regions of TB granulomas, we used a TB murine granuloma model in which NOS2 is absent. Abrogation of Arg1 expression in macrophages in this setting resulted in exacerbated lung granuloma pathology and bacterial burden. Arg1 expression in hypoxic granuloma regions correlated with decreased T-cell proliferation, suggesting that Arg1 regulation of T-cell immunity is involved in disease control. Our data argue that Arg1 plays a central role in the control of TB when NOS2 is rendered ineffective by hypoxia.
    Proceedings of the National Academy of Sciences of the United States of America. 09/2014;
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    ABSTRACT: The aryl hydrocarbon receptor (AhR) is a highly conserved ligand-dependent transcription factor that senses environmental toxins and endogenous ligands, thereby inducing detoxifying enzymes and modulating immune cell differentiation and responses. We hypothesized that AhR evolved to sense not only environmental pollutants but also microbial insults. We characterized bacterial pigmented virulence factors, namely the phenazines from Pseudomonas aeruginosa and the naphthoquinone phthiocol from Mycobacterium tuberculosis, as ligands of AhR. Upon ligand binding, AhR activation leads to virulence factor degradation and regulated cytokine and chemokine production. The relevance of AhR to host defence is underlined by heightened susceptibility of AhR-deficient mice to both P. aeruginosa and M. tuberculosis. Thus, we demonstrate that AhR senses distinct bacterial virulence factors and controls antibacterial responses, supporting a previously unidentified role for AhR as an intracellular pattern recognition receptor, and identify bacterial pigments as a new class of pathogen-associated molecular patterns.
    Nature 08/2014; · 38.60 Impact Factor
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    ABSTRACT: High-throughput analyses of RNA and protein expression are increasingly used for better understanding of vaccine-induced immunity and protection against infectious disease. With an increasing number of vaccine candidates in clinical development, it is timely to consider standardisation and harmonisation of sample collection, storage and analysis to ensure results of highest quality from these precious samples. These challenges were discussed by a group of international experts during a workshop organised by TRANSVAC, a European Commission-funded Research Infrastructure project. The main conclusions were: Platforms are rarely standardised for use in preclinical and clinical studies. Coordinated efforts should continue to harmonise the experimental set up of these studies, as well as the establishment of internal standards and controls. This will ensure comparability, efficiency and feasibility of the global analyses performed on preclinical and clinical data sets.
    Vaccine 07/2014; · 3.49 Impact Factor
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    ABSTRACT: Epithelioid, foam and multinucleated giant cells (MNGCs) are characteristics of tuberculosis (TB) granulomas, yet the precise genesis and functions of these transformed macrophages are unclear. We evaluated the role of platelets as drivers of macrophage transformation in mycobacterial infection.
    Journal of Infectious Diseases. 07/2014;
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    ABSTRACT: Bacillus Calmette-Guérin (BCG) has been used for vaccination against tuberculosis (TB) for nearly a century. Here we analyse immunity induced by a live TB vaccine candidate, recombinant BCG ΔureC::hly (rBCG), with proven pre-clinical and clinical safety and immunogenicity. We pursue in-depth analysis of the endogenous mycobacteria-specific CD4 T cell population, comparing the more efficacious rBCG with canonical BCG to determine which T memory responses are prerequisite for superior protection against TB. rBCG induced higher numbers and proportions of antigen-specific memory CD4 T cells than BCG, with a CXCR5(+)CCR7(+) phenotype and low expression of the effector transcription factors T-bet and Bcl-6. We find that superior protection of rBCG over BCG correlated with higher proportions and numbers of these central memory T cells, and increased T follicular helper cells associated with specific antibody responses. Adoptive transfer of mycobacteria-specific central memory T cells validated their critical role in protection against pulmonary TB.
    The Journal of infectious diseases. 06/2014;
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    ABSTRACT: Neutrophil trafficking to sites of inflammation is essential for the defense against bacterial and fungal infections, but also contributes to tissue damage in TH17-mediated autoimmunity. This process is regulated by chemokines, which often show an overlapping expression pattern and function in pathogen- and autoimmune-induced inflammatory reactions. Using a murine model of crescentic GN, we show that the pathogenic TH17/IL-17 immune response induces chemokine (C-X-C motif) ligand 5 (CXCL5) expression in kidney tubular cells, which recruits destructive neutrophils that contribute to renal tissue injury. By contrast, CXCL5 was dispensable for neutrophil recruitment and effective bacterial clearance in a murine model of acute bacterial pyelonephritis. In line with these findings, CXCL5 expression was highly upregulated in the kidneys of patients with ANCA-associated crescentic GN as opposed to patients with acute bacterial pyelonephritis. Our data therefore identify CXCL5 as a potential therapeutic target for the restriction of pathogenic neutrophil infiltration in TH17-mediated autoimmune diseases while leaving intact the neutrophil function in protective immunity against invading pathogens.
    Journal of the American Society of Nephrology : JASN. 06/2014;
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    ABSTRACT: The only tuberculosis (TB) vaccine in use today, bacillus Calmette-Guérin (BCG), provides insufficient protection and can cause adverse events in immunocompromised individuals, such as BCGosis in HIV+ newborns. We previously reported im-proved preclinical efficacy and safety of the recombinant vaccine candidate BCG ΔureC::hly, which secretes the pore-forming listeriolysin O of Listeria monocytogenes. Here, we evaluate a second-generation construct, BCG ΔureC::hly Δpdx1, which is de-ficient in pyridoxine synthase, an enzyme that is required for biosynthesis of the essential cofactor vitamin B6 . This candidate was auxotrophic for vitamin B6 in a concentration-dependent manner, as was its survival in vivo. BCG ΔureC::hly Δpdx1 showed markedly restricted dissemination in subcutaneously vaccinated mice, which was ameliorated by dietary supplementa-tion with vitamin B6 . The construct was safer in severe combined immunodeficiency mice than the parental BCG ΔureC::hly. A prompt innate immune response to vaccination, measured by secretion of interleukin-6, granulocyte colony-stimulating factor, keratinocyte cytokine, and macrophage inflammatory protein-1α, remained independent of vitamin B6 administration, while acquired immunity, notably stimulation of antigen-specific CD4 T cells, B cells, and memory T cells, was contingent on vitamin B 6 administration. The early protection provided by BCG ΔureC::hly Δpdx1 in a murine Mycobacterium tuberculosis aerosol challenge model consistently depended on vitamin B6 supplementation. Prime-boost vaccination increased protection against the canonical M. tuberculosis H37Rv laboratory strain and a clinical isolate of the Beijing/W lineage. We demonstrate that the efficacy of a profoundly attenuated recombinant BCG vaccine construct can be modulated by external administration of a small molecule. This principle fosters the development of safer vaccines required for immunocompromised individuals, notably HIV+ infants.
    mBio 06/2014; 5(3):e01262-14. · 6.88 Impact Factor
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    ABSTRACT: General interest in the biological functions of IFN type I in Mycobacterium tuberculosis (Mtb) infection increased after the recent identification of a distinct IFN gene expression signature in tuberculosis (TB) patients. Here we demonstrate that TB-susceptible mice lacking the receptor for IFN I (IFNAR1) were protected from death upon aerogenic infection with Mtb. Using this experimental model to mimic primary progressive pulmonary TB we dissected the immune processes affected by IFN I. IFNAR1 signaling did not affect T-cell responses, but markedly altered migration of inflammatory monocytes and neutrophils to the lung. This process was orchestrated by IFNAR1 expressed on both immune and tissue-resident radioresistant cells. IFNAR1-driven TB susceptibility was initiated by augmented Mtb replication and in situ death events, along with CXCL5/CXCL1-driven accumulation of neutrophils in alveoli, followed by the discrete compartmentalization of Mtb in lung phagocytes. Early depletion of neutrophils rescued TB-susceptible mice to levels observed in mice lacking IFNAR1. We conclude that IFN I alters early innate events at the site of Mtb invasion leading to fatal immunopathology. These data furnish a mechanistic explanation for the detrimental role of IFN I in pulmonary TB and form a basis for understanding the complex roles of IFN I in chronic inflammation.This article is protected by copyright. All rights reserved
    European Journal of Immunology 04/2014; · 4.97 Impact Factor
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    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).
  • Stefan H E Kaufmann
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    ABSTRACT: Tuberculosis (TB) remains a major health threat that will only be defeated by a combination of better drugs, diagnostics and vaccines. The only licensed TB vaccine, bacille Calmette-Guérin (BCG), protects against extrapulmonary TB in infants. Novel vaccine candidates that could protect against pulmonary TB either in TB naïve or in latent TB-infected healthy individuals have been developed and are currently being assessed in clinical trials. Subunit booster vaccines are either based on viral vectors expressing TB-specific antigens or on TB-protein antigens in adjuvants. Subunit vaccines are administered on top of BCG. Replacement vaccines for BCG are recombinant viable BCG or Mycobacterium tuberculosis. Several candidates are undergoing, or will soon start, phase IIb assessment for efficacy. The first vaccine candidate, MVA85A, to complete a phase IIb trial, unfortunately failed to show protection against TB in infants. Therapeutic vaccines composed of killed mycobacterial preparations target patients with complicated TB in adjunct to drug treatment. With increasing numbers of TB vaccine candidates in clinical trials, financial, regulatory and infrastructural issues arise, which would be best tackled by a global strategy. In addition, selection of the most promising vaccine candidates for further clinical development gains increasing importance.
    Current opinion in pulmonary medicine 03/2014; · 3.12 Impact Factor
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    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
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    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

Publication Stats

21k Citations
3,706.45 Total Impact Points


  • 1996–2014
    • Max Planck Institute for Infection Biology
      • Department of Immunology
      Berlín, Berlin, Germany
  • 2012
    • French National Centre for Scientific Research
      • Institute of Pharmacology and Structural Biology
      Lutetia Parisorum, Île-de-France, France
    • Leiden University Medical Centre
      • Department of Infectious Diseases
      Leiden, South Holland, Netherlands
    • Biomedical primate research centre
      • Parasitology
      Rijswijk, South Holland, Netherlands
    • Sokoine University of Agriculture (SUA)
      Murogoro, Morogoro Region, Tanzania
  • 2010–2012
    • Stellenbosch University
      • • Division of Molecular Biology and Human Genetics
      • • Department of Paediatrics and Child Health
      Stellenbosch, Province of the Western Cape, South Africa
    • Yale University
      • Department of Immunobiology
      New Haven, CT, United States
    • Research Center Borstel
      Borstel, Lower Saxony, Germany
    • Leibniz Institute for Farm Animal Biology
      Dummerstorf, Mecklenburg-Vorpommern, Germany
  • 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
  • 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
      Ashburn, Virginia, 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 Society
      München, Bavaria, 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
  • 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
  • 1995
    • Tokyo Metropolitan Institute of Public Health
      • Department of Veterinary Public Health
      Edo, Tōkyō, Japan
  • 1989
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 1987–1988
    • Max Planck Institute of Immunobiology and Epigenetics
      Freiburg, Baden-Württemberg, Germany
  • 1981–1984
    • Freie Universität Berlin
      Berlín, Berlin, Germany