Intracellular infection and immune system cues rewire adipocytes to acquire immune function

• DOI: 10.1016/j.cmet.2022.04.008
• Publication Date: 2022-05-03T14:56:54Z
• Authors: George Caputa; Mai Matsushita; David E. Sanin; Agnieszka M. Kabat; Joy Edwards-Hicks; Katarzyna M. Grzes; Roland Pohlmeyer; Michal A. Stanczak; Angela Castoldi; Jovana Cupovic; Aaron J. Forde; Petya Apostolova; Maximilian Seidl; Nikki van Teijlin...; Matteo Villa; Francesc Baixauli; Andrea Quintana; Alexandra Hackl; Lea Flachsmann; Fabian Hässler; Jonathan D. Curtis; Annette E. Patterson; Philipp Henneke; Erika L. Pearce; Edward J. Pearce
• Keywords: Killer Cells, Natural; 0301 basic medicine; Interferon-gamma; 03 medical and health sciences; Adipocytes; Immunity; 610; Cues; 3. Good health

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-γ 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-γ in perinodal AT (PAT). IFN-γ 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-γ and expression of iNOS. Thus, adipocytes are licensed by innate lymphocytes to acquire anti-bacterial functions during infection.