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

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 Teijlingen Bakker; 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

doi:10.1016/j.cmet.2022.04.008

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

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 Teijlingen Bakker, Matteo Villa, Francesc Baixauli, Andrea Quintana, Alexandra Hackl, Lea Flachsmann, Fabian HässlerJonathan D. Curtis, Annette E. Patterson, Philipp Henneke, Erika L. Pearce, Edward J. Pearce

School of Medicine

Research output: Contribution to journal › Article › peer-review

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-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.

Original language	English (US)
Pages (from-to)	747-760.e6
Journal	Cell Metabolism
Volume	34
Issue number	5
DOIs	https://doi.org/10.1016/j.cmet.2022.04.008
State	Published - May 3 2022

Keywords

IFN-γ
NK cells
NOD1
NOS2
adipocyte
iNK T cells
infection
lymph node
metabolism
perinodal adipose tissue

ASJC Scopus subject areas

Molecular Biology
Physiology
Cell Biology

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10.1016/j.cmet.2022.04.008

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Caputa, G., Matsushita, M., Sanin, D. E., Kabat, A. M., Edwards-Hicks, J., Grzes, K. M., Pohlmeyer, R., Stanczak, M. A., Castoldi, A., Cupovic, J., Forde, A. J., Apostolova, P., Seidl, M., van Teijlingen Bakker, N., Villa, M., Baixauli, F., Quintana, A., Hackl, A., Flachsmann, L., ... Pearce, E. J. (2022). Intracellular infection and immune system cues rewire adipocytes to acquire immune function. Cell Metabolism, 34(5), 747-760.e6. https://doi.org/10.1016/j.cmet.2022.04.008

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, van Teijlingen Bakker, N, Villa, M, Baixauli, F, Quintana, A, Hackl, A, Flachsmann, L, Hässler, F, Curtis, JD, Patterson, AE, Henneke, P, Pearce, EL & Pearce, EJ 2022, 'Intracellular infection and immune system cues rewire adipocytes to acquire immune function', Cell Metabolism, vol. 34, no. 5, pp. 747-760.e6. https://doi.org/10.1016/j.cmet.2022.04.008

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title = "Intracellular infection and immune system cues rewire adipocytes to acquire immune function",

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-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.",

keywords = "IFN-γ, NK cells, NOD1, NOS2, adipocyte, iNK T cells, infection, lymph node, metabolism, perinodal adipose tissue",

author = "George Caputa and Mai Matsushita and Sanin, {David E.} and Kabat, {Agnieszka M.} and Joy Edwards-Hicks and Grzes, {Katarzyna M.} and Roland Pohlmeyer and Stanczak, {Michal A.} and Angela Castoldi and Jovana Cupovic and Forde, {Aaron J.} and Petya Apostolova and Maximilian Seidl and {van Teijlingen Bakker}, Nikki and Matteo Villa and Francesc Baixauli and Andrea Quintana and Alexandra Hackl and Lea Flachsmann and Fabian H{\"a}ssler and Curtis, {Jonathan D.} and Patterson, {Annette E.} and Philipp Henneke and Pearce, {Erika L.} and Pearce, {Edward J.}",

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year = "2022",

month = may,

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doi = "10.1016/j.cmet.2022.04.008",

language = "English (US)",

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AU - Caputa, George

AU - Matsushita, Mai

AU - Sanin, David E.

AU - Kabat, Agnieszka M.

AU - Edwards-Hicks, Joy

AU - Grzes, Katarzyna M.

AU - Pohlmeyer, Roland

AU - Stanczak, Michal A.

AU - Castoldi, Angela

AU - Cupovic, Jovana

AU - Forde, Aaron J.

AU - Apostolova, Petya

AU - Seidl, Maximilian

AU - van Teijlingen Bakker, Nikki

AU - Villa, Matteo

AU - Baixauli, Francesc

AU - Quintana, Andrea

AU - Hackl, Alexandra

AU - Flachsmann, Lea

AU - Hässler, Fabian

AU - Curtis, Jonathan D.

AU - Patterson, Annette E.

AU - Henneke, Philipp

AU - Pearce, Erika L.

AU - Pearce, Edward J.

PY - 2022/5/3

Y1 - 2022/5/3

N2 - 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.

AB - 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.

KW - IFN-γ

KW - NK cells

KW - NOD1

KW - NOS2

KW - adipocyte

KW - iNK T cells

KW - infection

KW - lymph node

KW - metabolism

KW - perinodal adipose tissue

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SN - 1550-4131

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SP - 747-760.e6

JO - Cell Metabolism

JF - Cell Metabolism

IS - 5

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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