Max Planck Institute for Infection Biology

Berlin, Germany

Max Planck Institute for Infection Biology

Berlin, Germany

The Max Planck Institute for Infection Biology is a research institute of the Max Planck Society located in Berlin. The institute was founded 1993 near the Charité hospital in Berlin on the campus of the Humboldt University of Berlin in Berlin-Mitte. The Institute commenced its operation in a provisional laboratory facility and a small group of scientists that has greatly expanded over the years, and relocated to an especially built facility in summer 2000. The new facility is located in the heart of Berlin on the historical Charité medical campus, where Robert Koch and Emil Behring had made their important discoveries paving the field of infection research, in close proximity to the Parliament house and the newly constructed government offices. The choice of the location was to support the goal of the Institute to research infectious diseases in close collaboration with universities and clinical units. The Max Planck Society for the Advancement of Science is an independent, non-profit research organization that primarily promotes and supports research at its own institutes Wikipedia.

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News Article | May 10, 2017

A natural mechanism by which our cells kill the bacterium responsible for tuberculosis (TB) has been discovered by scientists at the Francis Crick Institute, which could help in the battle against antibiotic-resistant bacteria A natural mechanism by which our cells kill the bacterium responsible for tuberculosis (TB) has been discovered by scientists at the Francis Crick Institute, which could help in the battle against antibiotic-resistant bacteria. The findings, published in Cell Host & Microbe, could enable scientists to develop treatments for TB - one of the world's biggest health challenges - without the use of antibiotics, meaning that even antibiotic-resistant strains could be eliminated. The research was done in collaboration with scientists at the University of Oslo, the Max Planck Institute for Infection Biology in Germany and the Radboud Institute for Molecular Life Sciences in the Netherlands. "We are trying to better understand how our cells kill the bacteria with the idea of boosting people's natural defences in conjunction with conventional therapies to overcome TB," says Maximiliano Gutierrez, Group Leader at the Francis Crick Institute, who led the study. Immune cells called macrophages recognise and engulf Mycobacterium tuberculosis - the bacterium responsible for TB - securing it within tight-fitting internal compartments known as phagosomes. But before enzymes and toxic products can enter the phagosome to kill the bacterium, M. tuberculosis often escapes by puncturing holes in the phagosome membrane and leaking into the cell. In doing so, M. tuberculosis kills the cell and then feeds on its nutrients. By imaging the infection of cells with TB bacteria in real time, the team uncovered an innate mechanism that prevents M. tuberculosis from damaging phagosomes: the phagosomes are enlarged so that the bacterium can't easily reach and puncture holes in the membrane. This gives the cell enough time for bacteria-killing weapons to enter before the bacterium has a chance to escape. "We have known for a while that tight and spacious phagosomes exist, but it is only now becoming clear why there are two types," says Laura Schnettger, the first author of the paper and former PhD student in Maximiliano's lab at the Crick. By tagging different components in the macrophage with fluorescent markers, the team were able to see the enlarging of M. tuberculosis-containing phagosomes in real time under the microscope. They observed that M. tuberculosis failed to escape from these enlarged membrane sacs and that antibacterial components were delivered more efficiently. The team discovered that when macrophages are set to work engulfing M. tuberculosis, a protein known as Rab20 delivers additional membrane material to M. tuberculosis-containing phagosomes to enlarge them. "If you think of a cell as a city with lots of different types of transport then Rab proteins are the master regulators of public transport. They tell components in a cell where to go," explains Maximiliano. "Rab20 directs more membrane to the phagosome, enlarging it and preventing the bacteria from getting out." The team also analysed the typical coughed-up material from human patients with active TB. They found that these patients had more Rab20 in their body than people without TB, supporting the idea that Rab20 is important in fighting the TB infection. "A very high proportion of people that are likely exposed to M. tuberculosis, are able to clear the infection without developing full-blown TB," says Maximiliano. "It is possible that the body's natural mechanism to enlarge phagosomes plays a part in this." "The capture and escape of M. tuberculosis in cells is a highly dynamic process, so the only way you can understand what is going on is to image cells in real time at very high resolution. We are one of the few labs in the world that can perform long-term live cell imaging at sub-cellular resolution with the safety infrastructure required to work with a life-threatening bacterium."

Ottenhoff T.H.M.,Leiden University | Kaufmann S.H.E.,Max Planck Institute for Infection Biology
PLoS Pathogens | Year: 2012

In this review we discuss recent progress in the development, testing, and clinical evaluation of new vaccines against tuberculosis (TB). Over the last 20 years, tremendous progress has been made in TB vaccine research and development: from a pipeline virtually empty of new TB candidate vaccines in the early 1990s, to an era in which a dozen novel TB vaccine candidates have been and are being evaluated in human clinical trials. In addition, innovative approaches are being pursued to further improve existing vaccines, as well as discover new ones. Thus, there is good reason for optimism in the field of TB vaccines that it will be possible to develop better vaccines than BCG, which is still the only vaccine available against TB. © 2012 Ottenhoff, Kaufmann.

Gengenbacher M.,Max Planck Institute for Infection Biology | Kaufmann S.H.E.,Max Planck Institute for Infection Biology
FEMS Microbiology Reviews | Year: 2012

Tuberculosis (TB) remains a major health threat, killing nearly 2 million individuals around this globe, annually. The only vaccine, developed almost a century ago, provides limited protection only during childhood. After decades without the introduction of new antibiotics, several candidates are currently undergoing clinical investigation. Curing TB requires prolonged combination of chemotherapy with several drugs. Moreover, monitoring the success of therapy is questionable owing to the lack of reliable biomarkers. To substantially improve the situation, a detailed understanding of the cross-talk between human host and the pathogen Mycobacterium tuberculosis (Mtb) is vital. Principally, the enormous success of Mtb is based on three capacities: first, reprogramming of macrophages after primary infection/phagocytosis to prevent its own destruction; second, initiating the formation of well-organized granulomas, comprising different immune cells to create a confined environment for the host-pathogen standoff; third, the capability to shut down its own central metabolism, terminate replication, and thereby transit into a stage of dormancy rendering itself extremely resistant to host defense and drug treatment. Here, we review the molecular mechanisms underlying these processes, draw conclusions in a working model of mycobacterial dormancy, and highlight gaps in our understanding to be addressed in future research. © 2012 Federation of European Microbiological Societies.

Kaufmann S.H.E.,Max Planck Institute for Infection Biology
Seminars in Immunology | Year: 2013

Efforts over the last 2 decades have led to a rich research and development pipeline of tuberculosis (TB) vaccines. Although none of the candidates has successfully completed the clinical trial pipeline, many are under advanced clinical assessment. These vaccines aim at prevention of active TB, with most of them being considered for preexposure with recent additions for postexposure or multistage administration. A few therapeutic vaccines are under clinical assessment, as well. Preexposure vaccination with the licensed TB vaccine BCG prevents severe forms of TB in children but not in adolescents and adults. The current vaccine pipeline does not include strategies which prevent or eliminate infection with the causative agent Mycobacterium tuberculosis (Mtb). Rather in a best-case scenario, they are quantitatively superior to BCG in preventing active TB over prolonged periods of time, ideally lifelong in the face of latent Mtb infection. Qualitatively superior vaccines should be capable of preventing or eliminating Mtb infection, in this way eliminating the risk of TB reactivation. The time is now ripe to exploit radically new strategies to achieve this goal. © 2013.

Kaufmann S.H.E.,Max Planck Institute for Infection Biology
Immunity | Year: 2010

With almost a dozen vaccine candidates in clinical trials, tuberculosis (TB) research and development is finally reaping the first fruits of its labors. Vaccine candidates in clinical trials may prevent TB disease reactivation by efficiently containing the pathogen Mycobacterium tuberculosis (Mtb). Future research should target vaccines that achieve sterile eradication of Mtb or even prevent stable infection. These are ambitious goals that can be reached only by highly cooperative engagement of basic immunologists, vaccinologists, and clinical researchers-or in other words, by translation from basic immunology to vaccine research and development, as well as reverse translation of insights from clinical trials back to hypothesis-driven research in the basic laboratory. Here, we review current and future strategies toward the rational design of novel vaccines against TB, as well as the progress made thus far, and the hurdles that need to be overcome in the near and distant future. © 2010 Elsevier Inc.

Kaufmann S.H.E.,Max Planck Institute for Infection Biology
Trends in Immunology | Year: 2012

The past decade has witnessed a tremendous increase in the development of novel vaccines against tuberculosis (TB). In mice, each of these vaccine candidates stimulates an immune response that reduces the bacillary load, reflecting control but not sterilization of infection. Yet, the immune mechanisms underlying vaccine efficacy are only partially understood. In parallel to clinical assessment of current candidates, the next generation of vaccine candidates still needs to be developed. This requires basic research on how to induce the most efficacious immune response. Equally important is the dissection of immune responses in patients, latently infected healthy individuals, and participants of clinical vaccine trials. Amalgamation of this information will foster the way towards more efficacious vaccination strategies that not only prevent disease, but prevent or abolish infection. © 2012 Elsevier Ltd.

Amulic B.,Max Planck Institute for Infection Biology | Cazalet C.,Max Planck Institute for Infection Biology | Hayes G.L.,Max Planck Institute for Infection Biology | Metzler K.D.,Max Planck Institute for Infection Biology | Zychlinsky A.,Max Planck Institute for Infection Biology
Annual Review of Immunology | Year: 2012

Neutrophils are the most abundant white blood cells in circulation, and patients with congenital neutrophil deficiencies suffer from severe infections that are often fatal, underscoring the importance of these cells in immune defense. In spite of neutrophils' relevance in immunity, research on these cells has been hampered by their experimentally intractable nature. Here, we present a survey of basic neutrophil biology, with an emphasis on examples that highlight the function of neutrophils not only as professional killers, but also as instructors of the immune system in the context of infection and inflammatory disease. We focus on emerging issues in the field of neutrophil biology, address questions in this area that remain unanswered, and critically examine the experimental basis for common assumptions found in neutrophil literature. © 2012 by Annual Reviews. All rights reserved.

Kaufmann S.H.E.,Max Planck Institute for Infection Biology | Dorhoi A.,Max Planck Institute for Infection Biology
Current Opinion in Immunology | Year: 2013

Inflammation is critical for tuberculosis (TB) pathogenesis. The nonresolving aspect of inflammation in TB is caused by sophisticated intracellular survival strategies of tubercle bacilli. TB is a continuum comprising a spectrum of lesions as a consequence of complex regulation of inflammation. Proinflammatory cytokines, including interferons, tumor necrosis factor and interleukin 1 along with microRNAs and eicosanoids form an interactive network during TB. Cross-regulation between proinflammatory mediators strongly impacts on infected cell death patterns. These processes, in concert with local concentrations of proteases, such as cathepsins, serpins and matrix-metalloproteinases, affect tissue integrity, shape the architecture of granulomas and modulate tissue repair. With inflammation networks being uncovered in TB, the relevance of several pathways for novel interventions becomes clearer. © 2013 Elsevier Ltd.

Kaufmann S.H.E.,Max Planck Institute for Infection Biology
Current Opinion in Pulmonary Medicine | Year: 2014

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Kaufmann S.H.E.,Max Planck Institute for Infection Biology
The Lancet Infectious Diseases | Year: 2011

Tuberculosis is one of the most deadly infectious diseases. The situation is worsening because of co-infection with HIV and increased occurrence of drug resistance. Although the BCG vaccine has been in use for 90 years, protection is insufficient; new vaccine candidates are therefore needed. 12 potential vaccines have gone into clinical trials. Ten are aimed at prevention of tuberculosis and, of these, seven are subunit vaccines either as adjuvanted or viral-vectored antigens. These vaccines would be boosters of BCG-prime vaccination. Three vaccines are recombinant BCG constructs-possible replacements for BCG. Additional vaccine candidates will enter clinical trials in the near future, including postexposure vaccines for individuals with latent infection. In the long term, vaccines that prevent or eradicate infection with Mycobacterium tuberculosis would be the best possible option. Improved knowledge of immunology, molecular microbiology, cell biology, biomics, and biotechnology has paved the way towards an effective and safe vaccine against tuberculosis. The pipeline of new vaccine candidates from preclinical to clinical testing could be accelerated by development of biomarkers that can predict the clinical outcome of tuberculosis. © 2011 Elsevier Ltd.

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