The two most common causes of sepsis are pneumonia and peritonitis. Therefore, this research line focuses on these two infections. As part of this research studies are conducted on common forms of sepsis in tropical areas, in particular (caused by Burkholderia pseudomallei) and typhoid fever (caused by Salmonella typhi).
Observational studies in patients: The innate immune and procoagulant response is studied in various patient populations with sepsis. CEMM is the coordinating center of a large national sepsis consortium funded by CTMM (The Center for Translational and Molecular Medicine, a public-private consortium that comprises a multidisciplinary group of parties – universities, academic medical centers, medical technology enterprises and chemical and pharmaceutical companies). This CTMM project, entitled
“Molecular Diagnosis and Risk Stratification of Sepsis”or MARS, will enroll > 7000 patients admitted to the Intensive Care Units of the AMC and the UMC Utrecht; approximately one-third of these patients will have or will develop sepsis. The MARS project aims to generate tools that provide rapid and accurate information about an individual patient suffering from sepsis, including which microorganism is responsible for the infection and the severity and stage of the patient’s immune response. Other observational studies in patients with sepsis are conducted in , and . These studies focus on particular forms of sepsis (melioidosis in , typhoid fever in ) or on coinfection with HIV or malaria (). These clinical studies are performed in the broader context of pathogenetic studies in healthy humans and mice (see below).
Studies in healthy humans: The Infectious Diseases group frequently utilizes models in healthy humans to study mechanisms that underlie the activation of the innate immune and coagulation system. Roughly, these models make use of two distinct approaches: intravenous administration of l
ipopolysaccharide (component of the outer membrane of all Gram-negative bacteria) and bronchial instillation of lipopolysaccharide (using a bronchoscope). Interventions targeting either components of the innate immune system or the coagulation system provide insight into the role of these components in systemic (the intravenous model) and pulmonary (the bronchial model) inflammation and coagulation.
Studies in mice: The two most common causes of sepsis are pneumonia and peritonitis. The Infectious Diseases group uses several mouse models of pneumonia and peritonitis in order to obtain insight into the regulation of innate immunity and coagulation. Pneumonia is induced by intranasal inoculation with clinically relevant respiratory pathogens such as Streptococcus pneumoniae (the most common causative agent in community acquired pneumonia), Klebsiella pneumoniae,Pseudomonas aeruginosa, Haemophilus influenzae, Acinetobacter baumannii and Burkholderia pseudomallei. Peritonitis is induced by either intraperitoneal injection of Escherichia coli or by “cecal ligation and puncture”. In addition, CEMM works with a mouse model for typhoid fever. For this research, many different genetically modified mice are used, lacking either components of the innate immune system (e.g. Toll-like receptors) or of the coagulation system.
Recently, a study examining the expression of innate immune mechanism and procoagulant responses in patients with active tuberculosis was completed in Chittagong, (in collaboration with the Welcome Trust). In addition, this research line makes use of a mouse model of lung tuberculosis in which live Mycobacterium tuberculosis is instilled via the nose. This mouse model is very valuable for studying the pathogenesis of tuberculosis and potential novel treatment strategies. As such, this research line addresses questions that resemble those asked in the research line on sepsis. Moreover, using this model novel vaccine candidates for tuberculosis have been tested.
Members of the laboratory
- Tom van der Poll (group leader)
- Alex de Vos (staff)
- Kees van ‘t Veer (staff)
- Brendon Scicluna (postdoc)
- Joost Wiersinga (postdoc)
- Joppe Hovius (postdoc)
- Adam Anas (PhD student)
- Ahmed Achouiti (PhD student)
- Anne Jan van der Meer (PhD student)
- Arjan Hoogendijk (PhD student)
- Barry Mook (PhD student)
- Daan de Boer (PhD student)
- Dana Blok (PhD student)
- Floor van den Boogaard (PhD student)
- Gavin Koh (PhD student)
- Jolanda Lammers (PhD student)
- Katja de Jong (PhD student)
- Liesbeth Kager (PhD student)
- Lonneke van Vught (PhD student)
- Madelijn Geldhoff (PhD student)
- Marcel Schouten (PhD student)
- Maryse Wiewel (PhD student)
- Miriam van Lieshout (PhD student)
- Mischa Huson (PhD student)
- Tassili Weehuizen (PhD student)
- Tim Schuijt (PhD student)
- Tijmen Hommes (PhD student)
- Sacha de Stoppelaar (PhD student)
- Danielle Kruijswijk (technician)
- Miranda Versloot (technician)
- Regina de Beer (technician)
- Sanne Terpstra (technician