NeoSep
Macromolecular innate immune complexes in neonatal sepsis
In neonates the response of the innate immune system is critical for the initiation and maintenance of host defense. Altered inflammatory conditions, e.g. meningitis, are closely associated with neonatal sepsis. Gram negative bacteria such as E. coli and Gram positive bacteria such as Group B streptococci (GBS) induce the formation of cytokines by bacterial LPS and RNA respectively. GBS RNA instructs cytoplasmic macromolecular complex formation of Myeloid differentiation primary response gene 88, Toll-like receptors and inflammasomes containing inflammatory caspase.
Our project focuses on evidences of altered innate immune response during septic organ damage. We will experimentally analyze control mechanisms and regulations of multiprotein innate immune complex formation leading to the characteristic organ damage related inflammatory condition. We want to study properties of the innate immune complex as biomarker for neonatal sepsis and as an anti-inflammatory drug target. Furthermore, molecular determinants of complex formation and translocation across biological barriers will be studied. Results hence obtained will be translated for preterm born and very low birth weight infants at high risk for sepsis.