Darmflora

PRiming IMmunity At the
beginning of Life

PRIMAL

Darmflora

PRiming IMmunity At the beginning of Life

PRIMAL

Project 2

Immuno­metabolism

Role of the microbiome in metabolic macrophage programming and instruction of antimicrobial resistance at the beginning of life

Project Summary

Carbohydrate metabolism, i.e. whether oxidative phosphorylation or glycolysis predominates, impacts on the inflammatory phenotype of macrophages. Enhanced glycolysis characterizes inflammatory macrophages, and regulatory macrophages pre-dominantly use fatty acid oxidation (1). Oxygen tension impacts on metabolism. Normoxia promotes oxidative phosphorylation (Krebs cycle), and hypoxia promotes glycolysis for ATP production. Furthermore, bacterial metabolites such as butyrate drive the Krebs cycle, whereas lipopolysaccharide (LPS) promotesglycolysis. At the beginning of life, several cues potentially affect imunmetabolism, a) the transition from fetal hypoxia to a postnatal normoxia, b) bacterial colonization of the in utero largely sterile intestinal mucosa, c) replacement of embryonic macrophages s by monocyte-derived macrophages, and d) the nutritional provision of fatty acids. The complexity of these events impacts on the development of cellular intestinal immunity against potentially harmful bacteria like group B streptococcus (GBS), which commonly colonizes the neonatal intestinal lumen. We have previously shown that GBS interacts in a site specific fashion with macrophages (2), and we have dissected the macrophage autonomus response to Gram-positive bacteria both in humans and mice. In order to break new ground in understanding how the microbiome shapes metabolism and macrophage function an to identify therapeutic targets to promote host resistance, we propose to analyze, whether anti- and probiotics

  • alter macrophage development,
  • alter immunometaboliic properties of neonatal macrophages,
  • and immunometabolic changes impact on the resistance against invasive streptococcal infections.

Contact

Philipp Henneke

Koordinator des PRIMAL-Konsortiums

Prof. Dr. med. Philipp Henneke

Sektionsleiter Pädiatrische Infektiologie und Rheumatologie
Klinik für Allgemeine Kinder- und Jugendmedizin
Universitätsklinikum Freiburg
Mathildenstr. 1
D-79106 Freiburg

E-Mail: philipp.henneke@uniklinik-freiburg.de
Telefon: +49 (0) 761 270 77640
Telefax: +49 (0) 761 270 77600