Mannose-Binding Lectin is required for the effective clearance of apoptotic cells by adipose tissue macrophages during obesity

Published on Dec 1, 2014in Diabetes7.20
· DOI :10.2337/db14-0256
Rinke Stienstra29
Estimated H-index: 29
(Radboud University Nijmegen),
Wieneke Dijk9
Estimated H-index: 9
(WUR: Wageningen University and Research Centre)
+ 8 AuthorsSander Kersten65
Estimated H-index: 65
(WUR: Wageningen University and Research Centre)
Obesity is accompanied by the presence of chronic low-grade inflammation manifested by infiltration of macrophages into adipose tissue. Mannose-binding lectin (MBL), a soluble mediator of innate immunity, promotes phagocytosis and alters macrophage function. To assess the function of MBL in the development of obesity, we studied wild-type and MBL −/− mice rendered obese using a high-fat diet (HFD). Whereas no gross morphological differences were observed in liver, an HFD provoked distinct changes in the adipose tissue morphology of MBL −/− mice. In parallel with increased adipocyte size, MBL −/− mice displayed an increased influx of macrophages into adipose tissue. Macrophages were polarized toward an alternatively activated phenotype known to modulate apoptotic cell clearance. MBL deficiency also significantly increased the number of apoptotic cells in adipose tissue. Consistent with these observations, recombinant MBL enhanced phagocytic capacity of the stromal vascular fraction isolated from adipose tissue and modulated uptake of apoptotic adipocytes by macrophages. Despite changes in macrophage abundance and polarity, the absence of MBL did not affect systemic insulin resistance. Finally, in humans, lower levels of circulating MBL were accompanied by enhanced macrophage influx in subcutaneous adipose tissue. We propose a novel role for MBL in the recognition and clearance of apoptotic adipocytes during obesity.
  • References (44)
  • Citations (10)
Published on Nov 1, 2011in Nature Reviews Immunology44.02
Peter J. Murray64
Estimated H-index: 64
(St. Jude Children's Research Hospital),
Thomas A. Wynn93
Estimated H-index: 93
(NIH: National Institutes of Health)
Macrophages are strategically located throughout the body tissues, where they ingest and process foreign materials, dead cells and debris and recruit additional macrophages in response to inflammatory signals. They are highly heterogeneous cells that can rapidly change their function in response to local microenvironmental signals. In this Review, we discuss the four stages of orderly inflammation mediated by macrophages: recruitment to tissues; differentiation and activation in situ; conversion...
Published on Aug 1, 2011in Endocrinology3.80
Pamela Fischer-Posovszky25
Estimated H-index: 25
(University of Ulm),
Qiong A. Wang17
Estimated H-index: 17
(UTSW: University of Texas Southwestern Medical Center)
+ 2 AuthorsPhilipp E. Scherer111
Estimated H-index: 111
(UTSW: University of Texas Southwestern Medical Center)
Obesity is frequently associated with an infiltration of macrophages into adipose tissue. Adipocyte dysfunction causes a phenotypic switch of macrophages from an alternatively activated M2-like phenotype towards a proinflammatory M1 phenotype. The cross talk between adipocytes and infiltrating immune cells, in particular macrophages, is thought to contribute to local and eventually systemic inflammation. Here, we tested the phenotypic impact of a lack of adipocytes on the inflammatory status of ...
David L. Morris17
Estimated H-index: 17
Kanakadurga Singer15
Estimated H-index: 15
Carey N. Lumeng30
Estimated H-index: 30
Purpose of review Proinflammatory adipose tissue macrophages (ATMs) contribute to obesity-associated disease morbidity. We will provide an update of the current state of knowledge regarding the phenotypic and functional diversity of ATMs in lean and obese mice and humans.
Published on May 1, 2011in Cellular & Molecular Immunology8.21
Mingyong Wang2
Estimated H-index: 2
Yue Chen2
Estimated H-index: 2
+ 3 AuthorsZhengliang Chen9
Estimated H-index: 9
Mannan-binding lectin (MBL) plays a key role in the lectin pathway of complement activation and can influence cytokine expression. Toll-like receptor 4 (TLR4) is expressed extensively and has been demonstrated to be involved in lipopolysaccharide (LPS)-induced signaling. We first sought to determine whether MBL exposure could modulate LPS-induced inflammatory cytokine secretion and nuclear factor-κB (NF-κB) activity by using the monocytoid cell line THP-1. We then investigated the possible mecha...
Published on Feb 1, 2011in Immunology4.15
Melinda M. Dean13
Estimated H-index: 13
(Australian Red Cross Blood Service),
Robert L. Flower22
Estimated H-index: 22
(Australian Red Cross Blood Service)
+ 3 AuthorsSlavica Vuckovic22
Estimated H-index: 22
Mannose-binding lectin (MBL) is a serum lectin that plays a significant role in innate host defence. Individuals with mutations in exon 1 of the MBL2 gene have reduced MBL ligand binding and complement activation function and increased incidence of infection. We proposed that, during infection, MBL deficiency may impact on dendritic cell (DC) function. We analysed the blood myeloid DC (MDC) surface phenotype, inflammatory cytokine production and antigen-presenting capacity in MBL-deficient (MBL-...
Published on Nov 1, 2010in Human Immunology2.20
Shirley L. MacDonald11
Estimated H-index: 11
(Scottish National Blood Transfusion Service),
Ian Downing4
Estimated H-index: 4
(Scottish National Blood Transfusion Service)
+ 3 AuthorsDavid C. Kilpatrick20
Estimated H-index: 20
(Scottish National Blood Transfusion Service)
Abstract Mannan (or mannose)–binding lectin (MBL) can bind to monocytes and dendritic cells, but the significance of such interactions is unknown. We hypothesized that the presence of MBL might prevent the differentiation of monocytes into monocyte-derived dendritic cells or interfere with the development of dendritic cells in some way. We therefore investigated the influence of recombinant human MBL on surface antigen expression and on secretion of selected cytokines. By these means, no direct ...
Published on Oct 1, 2010in Trends in Immunology13.00
Denise A. Kaminski9
Estimated H-index: 9
(UR: University of Rochester),
Troy D. Randall58
Estimated H-index: 58
(UR: University of Rochester)
Studies of immunity typically focus on understanding how hematopoietic cells interact within conventional secondary lymphoid tissues. However, immune reactions and their regulation occur in various environments within the body. Adipose tissue is one tissue that can influence and be influenced by adjacent and embedded lymphocytes. Despite the abundance and wide distribution of such tissue, and despite a growing obesity epidemic, studies of these interactions have been only marginally appreciated ...
Published on Aug 1, 2010in Diabetes7.20
Yunhua L. Muller15
Estimated H-index: 15
Robert L. Hanson72
Estimated H-index: 72
+ 7 AuthorsLeslie J. Baier36
Estimated H-index: 36
Abstract Objective- MBL2 encodes the mannose-binding lectin which is a key player in the innate immune system, and has recently been found to play a role in insulin resistance and development of type 1 diabetes and gestational diabetes. To assess the role of MBL2 in diabetes susceptibility, this gene was analyzed in the Pima Indian population which has a high prevalence of type 2 diabetes. Research design and methods- Nineteen tag Single Nucleotide Polymorphisms (SNPs) were genotyped in a popula...
Published on Jun 1, 2010in Current Opinion in Lipidology4.84
Emily K. Anderson4
Estimated H-index: 4
Dario A. Gutierrez9
Estimated H-index: 9
Alyssa H. Hasty46
Estimated H-index: 46
(Vandy: Vanderbilt University)
Purpose of review In December of 2003, two seminal articles describing the presence of macrophages in obese adipose tissue were published. These adipose tissue macrophages (ATMs) are inflammatory and promote local and systemic insulin resistance. Due to the continuing rise in obesity around the world, understanding how these ATMs contribute to metabolic disorders is of much interest. Recent findings Chemokines have been extensively studied for their role in ATM recruitment. Deficiency or antagon...
Published on May 14, 2010in Journal of Biological Chemistry
Pingping Li25
Estimated H-index: 25
(UCSD: University of California, San Diego),
Min Lu16
Estimated H-index: 16
(UCSD: University of California, San Diego)
+ 11 AuthorsAnh Nguyen4
Estimated H-index: 4
(UCSD: University of California, San Diego)
Obesity represents a state of chronic, low grade inflammation and is associated with infiltration of increased numbers of adipose tissue macrophages (ATMs). Diet-induced obesity leads to an increase in non-inflammatory M1-like ATMs displaying the CD11c surface marker. We assessed the function of CD11c-positive ATMs when insulin resistant high fat diet (HFD) mice become insulin-sensitive after switching from HFD to normal chow (NC). HFD mice rapidly become insulin-sensitive in all major insulin-t...
Cited By10
Published on Apr 5, 2019in Seminars in Immunopathology6.80
Elise Dalmas (Paris Diderot University)
Growing evidence suggests that components of the innate immune system play a crucial role in regulating metabolic homeostasis. Macrophages were the primary immune cells to be described in both the white adipose tissue and the pancreatic islets. Therein, their functions, beneficial or detrimental, are extending under steady state and in the context of obesity-induced type 2 diabetes. Other populations, including innate lymphoid cells, are emerging as key sentinels of metabolic tissues and privile...
Published on Dec 1, 2018in Immunology4.15
Lucia Russo14
Estimated H-index: 14
(UM: University of Michigan),
Carey N. Lumeng30
Estimated H-index: 30
(UM: University of Michigan)
Published on Apr 1, 2018in Diabetologia7.11
Lily Boutens7
Estimated H-index: 7
(WUR: Wageningen University and Research Centre),
Guido Hooiveld37
Estimated H-index: 37
(WUR: Wageningen University and Research Centre)
+ 3 AuthorsRinke Stienstra29
Estimated H-index: 29
(WUR: Wageningen University and Research Centre)
Aims/hypothesis Recent studies have identified intracellular metabolism as a fundamental determinant of macrophage function. In obesity, proinflammatory macrophages accumulate in adipose tissue and trigger chronic low-grade inflammation, that promotes the development of systemic insulin resistance, yet changes in their intracellular energy metabolism are currently unknown. We therefore set out to study metabolic signatures of adipose tissue macrophages (ATMs) in lean and obese conditions.
Published on Jan 2, 2018in Journal of Experimental Medicine10.89
Megan L. Sulciner2
Estimated H-index: 2
Charles N. Serhan130
Estimated H-index: 130
+ 18 AuthorsJesmond Dalli42
Estimated H-index: 42
National Cancer Institute grants RO1 01CA170549-02 (to D. Panigrahy and C.N. Serhan), ROCA148633-01A4 (to D. Panigrahy), and GM095467 (to C.N. Serhan); the Stop and Shop Pediatric Brain Tumor Fund (to M.W. Kieran); the CJ Buckley Pediatric Brain Tumor Fund (to M.W. Kieran); Alex Lemonade Stand (to M.W. Kieran); Molly’s Magic Wand for Pediatric Brain Tumors (to M.W. Kieran); the Markoff Foundation Art-In-Giving Foundation (to M.W. Kieran); the Kamen Foundation (to M.W. Kieran); Jared Branfman Sun...
Published on Oct 1, 2017in Seminars in Cell & Developmental Biology5.46
José María Moreno-Navarrete29
Estimated H-index: 29
(ISCIII: Instituto de Salud Carlos III),
José Manuel Fernández-Real65
Estimated H-index: 65
(ISCIII: Instituto de Salud Carlos III)
Abstract The relationship among chronic low-grade inflammation, insulin resistance and other obesity-associated metabolic disturbances is increasingly recognized. The possible mechanisms that trigger these immunologic alterations remain to be fully understood. The complement system is a crucial element of immune defense system, being important in the activation of innate and adaptative immune response, promoting the clearance of apoptotic and damaged endogenous cells and participating in process...
Published on Nov 1, 2016in Immunological Reviews11.29
Myriam Martin12
Estimated H-index: 12
(Lund University),
Anna M. Blom53
Estimated H-index: 53
(Lund University)
Recognition and removal of apoptotic and necrotic cells must be efficient and highly controlled to avoid excessive inflammation and autoimmune responses to self. The complement system, a crucial part of innate immunity, plays an important role in this process. Thus, apoptotic and necrotic cells are recognized by complement initiators such as C1q, mannose binding lectin, ficolins, and properdin. This triggers complement activation and opsonization of cells with fragments of C3b, which enhances ph...
Published on Apr 13, 2016in Frontiers in Endocrinology3.63
Sung Sik Choe16
Estimated H-index: 16
(SNU: Seoul National University),
Jin Young Huh9
Estimated H-index: 9
(SNU: Seoul National University)
+ 2 AuthorsJae Bum Kim39
Estimated H-index: 39
(SNU: Seoul National University)
The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in per...
Published on Mar 1, 2016in Immunity21.52
Siamon Gordon114
Estimated H-index: 114
(University of Oxford)
It has been a century since the death of Elie Metchnikoff, who championed the role of phagocytosis in cellular immunity. Whereas others had observed the uptake of particles by cells from simple to complex organisms, he grasped its significance in the host response to injury and infection and established a firm basis for our understanding of inflammation and tissue homeostasis. The past century has brought improved tools of cellular and molecular biology to the study of phagocytosis and its contr...
Published on Feb 1, 2016in Experimental Dermatology2.87
Richard Wong7
Estimated H-index: 7
(University of Manchester),
Stefan Geyer18
Estimated H-index: 18
(Medical University of Vienna)
+ 2 AuthorsJason Wong38
Estimated H-index: 38
(University of Manchester)
The skin is often viewed as a static barrier that protects the body from the outside world. Emphasis on studying the skin's architecture and biomechanics in the context of restoring skin movement and function is often ignored. It is fundamentally important that if skin is to be modelled or developed, we do not only focus on the biology of skin but also aim to understand its mechanical properties and structure in living dynamic tissue. In this review, we describe the architecture of skin and patt...
Published on Jan 1, 2016in Molecular Immunology3.06
Stefanie Epp Boschmann2
Estimated H-index: 2
(UFPR: Federal University of Paraná),
Isabela Goeldner8
Estimated H-index: 8
(UFPR: Federal University of Paraná)
+ 3 AuthorsIara Messias-Reason14
Estimated H-index: 14
(UFPR: Federal University of Paraná)
Abstract Mannose-binding lectin (MBL) is a pattern recognition receptor of the lectin pathway of complement system. MBL binds to carbohydrates on microorganism’s surfaces leading to complement activation, opsonization and phagocytosis. Polymorphisms in the MBL gene ( MBL2 ) are associated with variations on MBL serum levels and with the susceptibility to various infectious and autoimmune diseases. The involvement of the lectin pathway in rheumatoid arthritis (RA) has been demonstrated by several...
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