Dynamics of Pattern-Recognition Receptors in the Systemic Inflammatory Response to Paediatric Heart Surgery with Cardiopulmonary Bypass

Objectives: Systemic inflammatory response syndrome (SIRS) following pediatric heart surgery is a commonly observed phenomenon. Although Pattern-recognition receptors (PRR) are of central importance for the innate immune response, little is known about their dynamics in children undergoing cardiovascular surgery. The aim of this study is to investigate the inflammatory response to congenital heart surgery with cardiopulmonary bypass (CPB) by describing the dynamic changes of Toll-like receptors (TLR) and Dectin-1 during the course of surgery and the first 48 hours after CPB. TLR2 and TLR4 respond primarily to bacterial components, while Dectin-1 mediates anti-fungal immunity.

Methods: Six children younger than two years of age undergoing planned surgery for congenital heart disease with CPB were examined. Patients with a cyanotic heart defect were excluded. Blood samples were obtained with written informed consent at 14 defined points in time. Surface expression of CD14, CD16, CD64, TLR2, TLR4, and Dectin-1 on leucocytes was determined by flow cytometry.

Results: TLR2 expression on neutrophils decreased until the end of CPB and reached preoperative values on the first postoperative day, even exceeding the 48 hours after CPB. A strong relationship could be observed between higher TLR2 expression on neutrophils 48 hours after CPB and an extended duration of hospital stay (R² = 0.83). Monocyte expression of TLR2 decreased until the end of surgery and reached a maximum 24 hours after CPB. Classical CD14++/CD16- monocytes returned to preoperative TLR2 levels, whereas TLR2 on inflammatory CD16+ monocytes were substantially increased 48 hours after CPB. Neutrophil TLR4 expression was hardly influenced by surgery contrary to previous findings in adults, while TLR4 expression on monocytes decreased until the end of surgery, before recovering 12 hours after CPB. Lowest Dectin-1 expression on neutrophils and classical CD14++/CD16- monocytes was found 12 hours after CPB. Even after 48 hours Dectin-1 still was below preoperative levels.

Conclusion: These data demonstrate the substantial impact of pediatric heart surgery with CPB on PRRs. Such changes in PRR expression patterns may be associated with worse outcome or stronger inflammatory response. To our knowledge, the expression of Dectin-1 during and after surgery is described for the first time. These findings have to be further evaluated and might provide prognostic markers or even new treatment approaches.