Unger lab

Background

Pneumonia, preterm birth and sepsis are some of the major causes of mortality in children under 5 years of age.

Pneumonia is the most common invasive infection of the respiratory tract. Suspicion of bacterial pneumonia is the most frequent reason to prescribe antibiotics in children. As viruses cause the majority of pneumonia in children, antibiotics are often prescribed unnecessarily. Incorrect and/or overuse of antibiotics can result in antibiotic resistance. For appropriate treatment of patients, it is thus important to rapidly define the pneumonia-causing pathogen. However, current minimal-invasive diagnostic methods do not discriminate bacterial from viral infections and they do not distinguish tissue-infecting pathogens from those that are harmlessly carried in the upper airways. Thus, a fast and minimal-invasive diagnostic tool that identifies the pneumonia-causing pathogen is warranted.

The most prevalent bacterial cause of community-acquired pneumonia in children is Mycoplasma pneumonia (Mp). Mp are relatively small bacteria (~300 nm) that lack a rigid cell wall. Although infections can be resolved there is no life-long protection. Apart from respiratory tract infections, extra-pulmonary 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.

Infection-related chorioamnionitis, or intrauterine infection, is one of the leading causes of preterm birth. Premature neonates are more vulnerable to infections such as sepsis and pneumonia, and the development of other morbidities such as bronchopulmonary disease in comparison to term born neonates. Early recognition and innovative treatment of chorioamnionitis and sepsis in preterm neonates will result in better outcomes.

The immature immune system in preterm neonates accounts for an important part of their increased susceptibility for sepsis. Better understanding of the neonatal immune response to bacteria could provide important clues for intervention strategies for sepsis in preterm neonates. Among bacteria associated with these severe conditions are Group B streptococcus, Staphylococcus aureus, E.coli and Ureaplasma.

Research aims and current research

The innate immune system is pivotal for the recognition of bacteria and to mount appropriate immunity to clear the infection. Bacterial infections in children can range from mild to severe, with neurological complications or sepsis as the most serious manifestations. Which patients are prone to develop a serious illness and why is unknown. Intriguingly, the same bacteria that can cause an infection, can also be asymptomatically carried at the mucosal surfaces of our body.

Our team uses patient and model based studies to obtain insight into the processes of bacterial infection and carriage in the mucosa as well as knowledge on the events that lead to complications. We examine these themes from both the pathogen and host perspective, and specifically the role of antigen presenting cells. With the results from these studies, we aim to develop novel approaches for precision diagnostics and targeted treatment of patients.

Research lines

1. Monocyte responses during bacterial infection and carriage in the airways.

2. Local and systemic antibody responses to Mycoplasma pneumoniae infection of and carriage on the respiratory tract.

3. Host-pathogen interactions during early onset sepsis in premature neonates.

4. Alternative treatments for respiratory infections with antibiotic-resistant bacteria.

Clinic

The very direct link with the clinic is of great value. Together with Prof. Dr. A.M.C. van Rossum, Pediatrician/Infectiologist, and Dr. H. M. Janssens, Pediatrician/Pulmonologist, we work in a bidirectional approach: key questions from the clinic concerning pathology, diagnosis and treatment of pneumonia and Cystic Fibrosis are translated to an experimental setting. Additionally, we collaborate with national and international groups to facilitate these basic and translational studies.

Selected references

Meyer Sauteur PM, de Bruijn ACJM, Graça C, Tio-Gillen AP, Estevão SC, Hoogenboezem T, Hendriks RW, Berger C, Jacobs BC, van Rossum AMC, Huizinga R, Unger WWJ. Antibodies to Protein but Not Glycolipid Structures Are Important for Host Defense against Mycoplasma pneumoniae. Infect Immun. 2019 Jan 24;87(2). pii: e00663-18.

Meyer Sauteur PM, de Groot RCA, Estevão SC, Hoogenboezem T, de Bruijn ACJM, Sluijter M, de Bruijn MJW, De Kleer IM, van Haperen R, van den Brand JMA, Bogaert D, Fraaij PLA, Vink C, Hendriks RW, Samsom JN, Unger WWJ, van Rossum AMC. The Role of B Cells in Carriage and Clearance of Mycoplasma pneumoniae From the Respiratory Tract of Mice. J Infect Dis. 2018 Jan 4;217(2):298-309.

de Groot RCA, Meyer Sauteur PM, Unger WWJ, van Rossum AMC. Things that could be Mycoplasma pneumoniae. J Infect. 2017 Jun;74 Suppl 1:S95-S100.

Jans J, Unger WWJ, Vissers M, Ahout IML, Schreurs I, Wickenhagen A, de Groot R, de Jonge MI, Ferwerda G. Siglec-1 inhibits RSV-induced interferon gamma production by adult T cells in contrast to newborn T cells.Eur J Immunol. 2018 Apr;48(4):621-631.

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. Carriage of Mycoplasma pneumoniae in the upper respiratory tract of symptomatic and asymptomatic children: an observational study. PLoS Med. 2013;10(5):e1001444.