Dermal adipocytes protect against invasive
            <i>Staphylococcus aureus</i>
            skin infection

Zhang, Ling-juan; Guerrero‐Juarez, Christian F.; Hata, Tissa; Bapat, Sagar P.; Ramos, Raúl; Plikus, Maksim V.; Gallo, Richard L.

doi:10.1126/science.1260972

Cited by 389 publications

(437 citation statements)

References 38 publications

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“…Resistin is expressed in monocytes and epithelial cells (26), and thus could also be involved in host defense against pathogenic infections. The bactericidal activity of resistin and its expression in adipose tissue are also consistent with the known role of adipocytes in producing antimicrobial proteins that protect the host from bacterial infection (32).…”

Section: Discussionsupporting

confidence: 55%

Resistin-like molecule β is a bactericidal protein that promotes spatial segregation of the microbiota and the colonic epithelium

Propheter

Chara

Harris

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

139

108

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The mammalian intestine is colonized by trillions of bacteria that perform essential metabolic functions for their hosts. The mutualistic nature of this relationship depends on maintaining spatial segregation between these bacteria and the intestinal epithelial surface. This segregation is achieved in part by the presence of a dense mucus layer at the epithelial surface and by the production of antimicrobial proteins that are secreted by epithelial cells into the mucus layer. Here, we show that resistin-like molecule β (RELMβ) is a bactericidal protein that limits contact between Gram-negative bacteria and the colonic epithelial surface. Mouse and human RELMβ selectively killed Gram-negative bacteria by forming size-selective pores that permeabilized bacterial membranes. In mice lacking RELMβ, Proteobacteria were present in the inner mucus layer and invaded mucosal tissues. Another RELM family member, human resistin, was also bactericidal, suggesting that bactericidal activity is a conserved function of the RELM family. Our findings thus identify the RELM family as a unique family of bactericidal proteins and show that RELMβ promotes host-bacterial mutualism by regulating the spatial segregation between the microbiota and the intestinal epithelium.antibacterial protein | microbiota | innate immunity | intestinal epithelium

show abstract

Section: Discussionsupporting

confidence: 55%

Resistin-like molecule β is a bactericidal protein that promotes spatial segregation of the microbiota and the colonic epithelium

Propheter

Chara

Harris

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

139

108

View full text Add to dashboard Cite

show abstract

“…In addition, all RDEB mice were cocolonized with one or multiple additional bacteria (SI Appendix, Table S2). Furthermore, previous proteomic studies on RDEB skin had revealed a significant increase in abundance of the antimicrobial peptide Camp (3), which has been implicated to play an important role in defense against invasive Staphylococcus aureus infections (24). Thus, RDEB mice were able to respond to Staphylococcus aureus by increased production of antimicrobial peptides, yet the bacterial colonization was elevated.…”

Section: Elevated Bacterial Colonization Of Rdeb Skin Is Independent Onmentioning

confidence: 93%

Impaired lymphoid extracellular matrix impedes antibacterial immunity in epidermolysis bullosa

Nyström

Bornert

Kühl

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB), a skin fragility disorder that, unexpectedly, manifests also with elevated colonization of commensal bacteria and frequent wound infections. Here, we describe an unprecedented systemic function of collagen VII as a member of a unique innate immune-supporting multiprotein complex in spleen and lymph nodes. In this complex, collagen VII specifically binds and sequesters the innate immune activator cochlin in the lumen of lymphoid conduits. In genetic mouse models, loss of collagen VII increased bacterial colonization by diminishing levels of circulating cochlin LCCL domain. Intraperitoneal injection of collagen VII, which restored cochlin in the spleen, but not in the skin, reactivated peripheral innate immune cells via cochlin and reduced bacterial skin colonization. Systemic administration of the cochlin LCCL domain was alone sufficient to diminish bacterial supercolonization of RDEB mouse skin. Human validation demonstrated that RDEB patients displayed lower levels of systemic cochlin LCCL domain with subsequently impaired macrophage response in infected wounds. This study identifies an intrinsic innate immune dysfunction in RDEB and uncovers a unique role of the lymphoid extracellular matrix in systemic defense against bacteria.collagen VII | innate immunity | bacteria | recessive dystrophic epidermolysis bullosa | cochlin

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“…In addition to its metabolic role as a depot of lipids and lipid-soluble vitamins, it has steroidogenic activity and synthesizes hormones and paracrine mediators that control appetite, lipid and carbohydrate metabolism and reproduction (Cinti 2012). Moreover, adipose tissue is involved in immune surveillance (Grant and Dixit 2015;Zhang et al 2015). This group of functions suggests that the adipose tissue depots act as an integrated metabolic, endocrine and immune organ of the body (Ferrante 2013;Galic et al 2010;Rosen and Spiegelman 2014).…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue macrophages in non-rodent mammals: a comparative study

et al. 2015

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The stromal vascular fraction (SVF) of adipose tissue in rodents and primates contains mesenchymal stem cells and immune cells. SVF cells have complex metabolic, immune and endocrine functions with biomedical impact. However, in other mammals, the amount of data on SVF stem cells is negligible and whether the SVF hosts immune cells is unknown. In this study, we show that the SVF is rich in immune cells, with a dominance of adipose tissue macrophages (ATMs) in cattle (Bos primigenius taurus), domestic goat (Capra aegagrus hircus), domestic sheep (Ovis aries), domestic cat (Felis catus) and domestic dog (Canis familiaris). ATMs of these species are granulated lysosome-rich cells with lamellipodial protrusions and express the lysosome markers acid phosphatase 5 (ACP-5) and Mac-3/Lamp-2. Using ACP-5 and Mac-3/Lamp-2 as markers, we additionally detected ATMs in other species, such as the domestic horse (Equus ferus caballus), wild boar (Sus scrofa) and red fox (Vulpes vulpes). Feline and canine ATMs also express the murine macrophage marker F4/80 antigen. In the lean condition, the alternative macrophage activation marker CD206 is expressed by feline and canine ATMs and arginase-1 by feline ATMs. Obesity is associated with interleukin-6 and interferon gamma expression and with overt tyrosine nitration in both feline and canine ATMs. This resembles the obesity-induced phenotype switch of murine and human ATMs. Thus, we show, for the first time, that the presence of ATMs is a general trait of mammals. The interaction between the adipose cells and SVF immune cells might be evolutionarily conserved among mammals.

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Dermal adipocytes protect against invasive Staphylococcus aureus skin infection

Cited by 389 publications

References 38 publications

Resistin-like molecule β is a bactericidal protein that promotes spatial segregation of the microbiota and the colonic epithelium

Resistin-like molecule β is a bactericidal protein that promotes spatial segregation of the microbiota and the colonic epithelium

Impaired lymphoid extracellular matrix impedes antibacterial immunity in epidermolysis bullosa

Adipose tissue macrophages in non-rodent mammals: a comparative study

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