Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Caputa, G; Matsushita, M; Sanin, DE; Kabat, AM; Edwards-Hicks, J; Grzes, KM; Pohlmeyer, R; Stanczak, MA; Castoldi, A; Cupovic, J; Forde, AJ; Apostolova, P; Seidl, M; Bakker, NV; Villa, M; Baixauli, F; Quintana, A; Hackl, A; Flachsmann, L; Hassler, F; Curtis, JD; Patterson, AE; Henneke, P; Pearce, EL; Pearce, EJ.
Intracellular infection and immune system cues rewire adipocytes to acquire immune function
CELL METAB. 2022; 34(5): 747-+.
Doi: 10.1016/j.cmet.2022.04.008
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Villa Matteo
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- Abstract:
- Adipose tissue (AT) plays a central role in systemic metabolic homeostasis, but its function during bacterial infection remains unclear. Following subcutaneous bacterial infection, adipocytes surrounding draining lymph nodes initiated a transcriptional response indicative of stimulation with IFN-g and a shift away from lipid metabolism toward an immunologic function. Natural killer (NK) and invariant NK T (iNKT) cells were identified as sources of infection-induced IFN-g in perinodal AT (PAT). IFN-g induced Nos2 expression in adipocytes through a process dependent on nuclear-binding oligomerization domain 1 (NOD1) sensing of live intracellular bacteria. iNOS expression was coupled to metabolic rewiring, inducing increased diversion of extracellular L-arginine through the arginosuccinate shunt and urea cycle to produce nitric oxide (NO), directly mediating bacterial clearance. In vivo, control of infection in adipocytes was dependent on adipocyte-intrinsic sensing of IFN-g and expression of iNOS. Thus, adipocytes are licensed by innate lymphocytes to acquire anti-bacterial functions during infection.