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

• Published in: Cell metabolism Vol. 34; no. 5; pp. 747 - 760.e6
• Main Authors: Caputa, George, Matsushita, Mai, Sanin, David E., Kabat, Agnieszka M., Edwards-Hicks, Joy, Grzes, Katarzyna M., Pohlmeyer, Roland, Stanczak, Michal A., Castoldi, Angela, Cupovic, Jovana, Forde, Aaron J., Apostolova, Petya, Seidl, Maximilian, van Teijlingen Bakker, Nikki, Villa, Matteo, Baixauli, Francesc, Quintana, Andrea, Hackl, Alexandra, Flachsmann, Lea, Hässler, Fabian, Curtis, Jonathan D., Patterson, Annette E., Henneke, Philipp, Pearce, Erika L., Pearce, Edward J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03-05-2022
• Subjects: adipocyte; IFN-γ; infection; iNK T cells; lymph node; metabolism; NK cells; NOD1; NOS2; perinodal adipose tissue; infection; IFN-γ; NK cells; iNK T cells; NOS2; lymph node; perinodal adipose tissue; adipocyte; NOD1; metabolism
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2022.04.008

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.
[Display omitted]
•NK and iNKT cells make IFN-γ in response to bacterial infection in PAT•IFN-γ induces NOD1-dependent iNOS expression in infected adipocytes•Metabolic reprograming supports NO production in infected adipocytes•Intrinsic NO production allows adipocytes to clear intracellular bacteria
Caputa and Matsushita et al. explored the role of perinodal adipose tissue (PAT) in the immune response to distal bacterial infection. They found that the infection spread to PAT, causing local IFN-γ- and NOD1-dependent Nos2 expression by adipocytes, and the repurposing of these cells away from lipid metabolism toward fighting infection.