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Infection and Immunity - Unger lab

Infection and Immunity - Unger lab

Background


In children, pneumonia is the most common invasive infection of the respiratory tract and the number one cause of mortality in children worldwide. Since there is no fast and minimally invasive diagnostic tool to identify the pneumonia-causing pathogens, suspected pneumonia is an important reason to prescribe antibiotics. However, the majority of lung infections are caused by viruses, for which antibiotics are ineffective. Antibiotic resistance from overuse of antibiotics is a major problem and is mainly caused by the lack of proper diagnosis. A major problem of all current diagnostic tests in pneumonia is that they are not only positive in infected children, but also in healthy children carrying the potential pathogen without any symptoms.

The most prevalent bacterial cause of community-acquired pneumonia in children is Mycoplasma pneumonia (Mp). Its pathogenesis however is still unclear. Mp are relatively small bacteria (~300 nm) and lack a rigid cell wall. Although infections can be resolved there is no life-long protection, which may be related to antigenic variation between Mp strains.
Apart from respiratory tract infections, extrapulmonary manifestations, as a result of either direct infection or immune-mediated events, occur in up to 25% of Mp infections. Nervous system disease is one of the most common and severe complications. If Mp actually accesses the central nervous system is unknown.
We recently found that Mp infections are associated with the Guillain Barré syndrome, an acute post-infectious immune-mediated polyneuropathy caused by antibodies that cross-react with glycolipid structures on myelin sheets of peripheral nerve cells. Our recent data suggest that the development of such cross-reactive antibodies can be elicited by Mp infections.

Vaccination is an attractive alternative to antibiotics in the combat against infections with Mp as well as other respiratory pathogens. However, the development of vaccines has been hindered by conflicting data regarding the role of B cells in immunity against Mp.


Research aims and current research

The research of our group is aimed at finding novel targets for treatment and/or development of protective vaccines against respiratory pathogens, and for Mp in particular. Hereto in vivo, in vitro and in situ models are used.

Current research lines include 

  1. Insight in the pathogenesis of Mp;
  2. The development of a more accurate method to demonstrate the causative agent of pneumonia as well as to discern pathogen colonization from infection;
  3. Unravel what pathogenic structures and events during Mp infections result in normal vs pathological B cell activation and antibody responses;
  4. Notch signaling mediating the barrier function of brain endothelial cells in homeostasis and inflammation;
  5. Define the immunogenic structures in Mp to develop a protecting vaccine;
  6. Development of vaccines for respiratory infections and explore "patient-friendly" administration routes

To facilitate these basic and translational studies, we work closely together with national and international collaborators.

Clinic

The very direct link with the clinic is of great value. Together with Dr. A.M.C. van Rossum, Pediatrician/Infectiologist, we work in a bidirectional approach: key questions from the clinic concerning pathology, diagnosis and treatment of pneumonia are translated to an experimental setting.

Selected references

  1. Meyer Sauteur PM, Unger WW, Nadal D, Berger C, Vink C, van Rossum AM. 2016. Infection with and carriage of Mycoplasma pneumoniae in Children. Front Microbiol.7:329.
  2. Meyer Sauteur PM, Jacobs BC, Spuesens EB, Jacobs E, Nadal D, Vink C, van Rossum AM. 2014. Antibody responses to Mycoplasma pneumoniae: role in pathogenesis and diagnosis of encephalitis? PLoS Pathog.10(6):e1003983.
  3. Meyer Sauteur PM, Roodbol J, Hackenberg A, de Wit MC, Vink C, Berger C, Jacobs E, van Rossum AM, Jacobs BC. 2015. Severe childhood Guillain-Barré syndrome associated with Mycoplasma pneumoniae infection: a case series. J Peripher Nerv Syst. 20(2):72-8.
  4. Spuesens EB, Fraaij PL, Visser EG, Hoogenboezem T, Hop WC, van Adrichem LN, Weber F, Moll HA, Broekman B, Berger MY, van Rijsoort-Vos T, van Belkum A, Schutten M, Pas SD, Osterhaus AD, Hartwig NG, Vink C, van Rossum AM. 2013. Carriage of Mycoplasma pneumoniae in the upper respiratory tract of symptomatic and asymptomatic children: an observational study. PLoS Med. 10(5):e1001444.
  5. Streng-Ouwehand I, Ho NI, Litjens M, Kalay H, Boks MA, Cornelissen LA, Kaur Singh S, Saeland E, Garcia-Vallejo JJ, Ossendorp FA, Unger WW, van Kooyk Y. 2016. Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells. Elife 5. pii: e11765.
  6. Boks MA, Unger WW, Engels S, Ambrosini M, van Kooyk Y, Luttge R. 2015. Controlled release of a model vaccine by nanoporous ceramic microneedle arrays. Int J Pharm. 491(1-2):375-83.
  7. Unger WW, van Kooyk Y. 2011. 'Dressed for success' C-type lectin receptors for the delivery of glyco-vaccines to dendritic cells. Curr Opin Immunol. 23(1):131-7

Click here for all publications by Wendy Unger


Group members

Wendy Unger (PhD, assistant professor)
Patrick Meyer-Sauteur (MD, PhD student)
Ruben de Groot (MD, PhD student)
Theo Hoogenboezem (technician)
Ad de Bruijn (technician)
Silvia Estevão (technician)