Necrosis Driven Triglyceride Synthesis Primes Macrophages for Inflammation During Mycobacterium tuberculosis Infection.

Frontiers in Immunology
Neetika JaisinghaniSheetal Gandotra

Abstract

Pulmonary tuberculosis (TB) exhibits granulomatous inflammation, a site of controlling bacterial dissemination at the cost of host tissue damage. Intrigued by the granuloma type-dependent expression of inflammatory markers in TB, we sought to investigate underlying metabolic changes that drive amplification of inflammation in TB. Here, we show an association of higher inflammation in necrotic granulomas with the presence of triglyceride (TG)-rich foamy macrophages. The conspicuous absence of these macrophages in solid granulomas identified a link between the ensuing pathology and the metabolic programming of foamy macrophages. Consistent with in vivo findings, in vitro infection of macrophages with Mycobacterium tuberculosis (Mtb) led to increase in TG synthesis only under conditions of ~60% necrosis. Genetic and pharmacologic intervention that reduced necrosis prevented this bystander response. We further demonstrate that necrosis independent of Mtb also elicits the same bystander response in human macrophages. We identified a role for the human enzyme involved in TG synthesis, diacylglycerol O-acyltransferase (DGAT1), in this phenomenon. The increased TG levels in necrosis-associated foamy macrophages promoted the pro-inflamm...Continue Reading

References

Aug 19, 2000·The Journal of Biological Chemistry·D L BrasaemleC Londos
Dec 24, 2002·Infection and Immunity·Carrie J Riendeau, Hardy Kornfeld
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Laura L ListenbergerJean E Schaffer
May 10, 2005·Bioorganic & Medicinal Chemistry Letters·Kosuke DodoMikiko Sodeoka
Dec 21, 2005·Brain : a Journal of Neurology·Leonie A BovenJon D Laman
Oct 21, 2006·The Journal of Clinical Investigation·Hang ShiJeffrey S Flier
Sep 7, 2007·The European Respiratory Journal·A M B MenezesUNKNOWN Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) Team
Mar 8, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Elena RigamontiBart Staels
Sep 2, 2008·Journal of Lipid Research·Chi-Liang Eric YenRobert V Farese
Mar 24, 2009·Annual Review of Immunology·Andrea M Cooper
May 14, 2009·The Journal of Clinical Investigation·Hannelie KorfKris Huygen
Jun 30, 2009·Nature Immunology·Maziar DivangahiHeinz G Remold
Dec 1, 2009·Cell·Robert V Farese, Tobias C Walther
Jan 30, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Eric A SchwartzPeter D Reaven
Feb 4, 2010·The Journal of Clinical Investigation·Suneil K KoliwadRobert V Farese
Jul 3, 2010·EMBO Molecular Medicine·Mi-Jeong KimDavid G Russell
Jan 12, 2013·The Journal of Biological Chemistry·Wonsik LeeDavid G Russell
Mar 23, 2013·Annual Review of Immunology·Anne O'GarraMatthew P R Berry
Jun 8, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hedwin Kitdorlang DkharPawan Gupta
Nov 5, 2014·Nature Reviews. Cardiology·Giulia Chinetti-GbaguidiBart Staels
Dec 19, 2014·Nature Immunology·Ian M OrmeAndrea M Cooper
Jan 24, 2015·Nature Reviews. Immunology·Alan R Tall, Laurent Yvan-Charvet

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Citations

Aug 1, 2020·Pathogens·Paige E Allen, Juan J Martinez
Aug 6, 2020·Frontiers in Microbiology·Pooja AgarwalFernando O Martinez
Aug 17, 2020·Nature Communications·Angela CastoldiEdward J Pearce
Jan 24, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kasparas PetkeviciusAntonio Vidal-Puig
Jan 27, 2021·Annual Review of Pathology·Rachel L KinsellaChristina L Stallings
Jun 3, 2021·Autophagy·Tanushree MukherjeeKithiganahalli Narayanaswamy Balaji
May 27, 2021·FEMS Microbiology Reviews·Ivy MallickStéphane Canaan
Jun 25, 2021·The Journal of Cell Biology·Marta BoschAlbert Pol
Jan 8, 2021·ACS Applied Materials & Interfaces·Sarita MishraMunia Ganguli

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Methods Mentioned

BETA
PMA
confocal microscopy
Fluorescence
ELISA

Software Mentioned

Volocity
Image Quant
IN CELL Developer
ImageJ
Leica LAX
LipidTox

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