Filarial Infection or Antigen Administration Improves Glucose Tolerance in Diet-Induced Obese Mice

Berbudi, Afiat; Surendar, Jayagopi; Ajendra, Jesuthas; Gondorf, Fabian; Schmidt, D; Neumann, Anna-Lena; Wardani, Ajeng P.F.; Layland, Laura E.; Hoffmann, Laura; Pfeifer, Alexander; Hoerauf, Achim; Hübner, Marc P.

doi:10.1159/000448401

Cited by 61 publications

(88 citation statements)

References 54 publications

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“…Therefore it is difficult to know if the increased eosinophils in WAT were responsible for the reduced weight and improved glucose tolerance, or if the weight of the mouse was influenced by the systemic increases in eosinophils that occur throughout the rest of the IL-5tg mouse, which then accounted for improved glucose homeostasis. Several studies have used alternative ways to increase WAT eosinophils, such as the parasitic infection model [14,94,104,109,111,112]. Yet again, the question must be asked whether weight loss simply occurred due to the mouse being energetically taxed while clearing an infection.…”

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confidence: 99%

“…In ΔdblGATA and IL-5 -/-transgenic mouse lines, which have a near complete absence of eosinophils, HFD feeding resulted in greater glucose intolerance compared to wildtype mice [32,94,111]. Thus, while it is difficult to be confident that increasing WAT eosinophils over baseline improves glucose tolerance, depleting eosinophils negatively impacts glucose tolerance in all published studies to date.…”

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confidence: 99%

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Contributions of innate type 2 inflammation to adipose function

Bolus

Hasty

2019

Journal of Lipid Research

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A critical contributor to health consequences of the obesity epidemic is dysregulated adipose tissue (AT) homeostasis. While white, brown, and beige AT function are all altered in obesity-related disease, white AT is marked by progressive inflammation & adipocyte dysfunction and has been the focus of extensive "immunometabolism" research in the past decade. The exact triggering events initiating and sustaining AT inflammation are still under study, but it has been shown that reducing inflammation improves insulin action in AT. Scientific efforts continue seeking interventions to mitigate obesity-associated AT inflammation, and many groups are now determining how lean healthy AT homeostasis is maintained in order to leverage these mechanisms as therapeutic targets. Such studies have revealed an elaborate network of immune cells, cytokines, and other cellular mediators coordinate AT function. Recent studies elucidated the involvement of the innate immune system in AT homeostasis (e.g. beiging and insulin sensitivity), including M2-like macrophages, eosinophils, innate lymphoid type 2 cells, and several others. In this review, we summarize the existing literature on innate type 2 inflammation in AT; additionally we draw attention to areas of debate where seemingly conflicting data promises to yield more surprising and elegant biology as studies continue to dissect AT physiology. prospective analyses of nearly a million adults, showed that obesity can decrease a person's life span up to 10 years [7]. Thus, a better understanding of adipose tissue (AT), the organ that expands the most in size during obesity, should provide solutions to this health concern.When discussing AT, white adipose tissue (WAT) is most commonly considered; however, other types of AT, brown adipose tissue (BAT) and beige AT also exist.Adipocytes in WAT and BAT are generated from unique progenitors. WAT stores excess energy in the form of triglycerides. BAT can store small amounts of triglycerides; however, its primary role is to burn fatty acids to generate heat. Beige fat has brown-like properties but is transiently present in WAT depots (especially subcutaneous) upon beta-adrenergic stimulation. Regulation of all three of these fat depots is critically important for lipid and energy homeostasis.WAT consists of spatially distinct beds: visceral, omental, subcutaneous, perivascular, epicardial, and many others. These depots serve to cushion organs they BAT is localized primarily in subscapular regions in rodents, and was only discovered in adult humans in the past decade [10,11]. BAT has a characteristic brown appearance grossly, and is easily distinguished from WAT. This distinctive color is due to the presence of concentrated mitochondria within each brown adipocyte, accompanied by high iron concentrations required for activation of the electron transport chain during beta-oxidation. High expression of uncoupling protein 1 (UCP-1) causes this beta-oxidation to result in generation of heat rather than ATP (thermogenesis), thus assistin...

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confidence: 99%

Section: Downloaded Frommentioning

confidence: 99%

Contributions of innate type 2 inflammation to adipose function

Bolus

Hasty

2019

Journal of Lipid Research

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“…Studies in animal models and in humans have indicated that helminths might play a protective role in the development of allergies, autoimmunities and inflammatory bowel disease . Moreover, recent in vivo studies showed that helminth infections might protect against insulin resistance as helminth‐induced Th2 responses were associated with improved glucose metabolism and insulin signalling in mice …”

Section: Introductionmentioning

confidence: 99%

The effect of three‐monthly albendazole treatment on Th2 responses: Differential effects on IgE and IL‐5

Ruiter

Tahapary

Wammes

et al. 2017

Parasite Immunology

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Helminth parasites induce a strong Th2 response, characterized by high levels of IgE and elevated signature cytokines such as IL-5. As many global deworming programmes are underway, there is concern that this might lead to emergence of Th1-mediated pathologies when the counterbalancing helminth-induced Th2 response is absent. Therefore, we assessed the effect of deworming on Th2-mediated responses in a household-clustered randomized controlled trial in Indonesia. Total plasma IgE and whole-blood IL-5 responses to mitogen phytohaemagglutinin (PHA) were measured in 1494 and 682 subjects, respectively, at baseline, 9 and 21 months after three-monthly single-dose treatment with albendazole or placebo. Anthelmintic treatment did not result in complete removal of helminth infections in the community. However, treatment significantly decreased IgE levels in albendazole- compared to placebo-treated subjects. IL-5 responses to PHA were not significantly affected by anthelmintic treatment and tended to increase in albendazole-treated subjects, indicating that intensive treatment of helminth parasites has different outcomes on B-cell (IgE levels) and T-cell (IL-5) responses. The data shows that 2 years of deworming can have differential effects on responses typified as Th2-mediated, which needs to be taken into account when examining the impact of helminths on noncommunicable diseases.

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“…sigmodontis worms (LsAg) induce type 2 and regulatory immune responses in mice. The described modulation of the immune system protects mice against the onset of type 1 diabetes (16–18) and improves diet‐induced glucose intolerance in obese mice (19).…”

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confidence: 99%

Filarial extract ofLitomosoides sigmodontisinduces a type 2 immune response and attenuates plaque development in hyperlipidemic ApoE‐knockout mice

et al. 2019

Self Cite

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A type 1 immune response is involved in atherosclerosis progression, whereas the role of a type 2 polarization, especially with regard to an enhanced T helper (Th)2 cell differentiation, is still unclear. Helminths trigger type 2 immune responses, protecting the host from inflammatory disorders. We investigated whether an increased type 2 polarization by administration of Litomosoides sigmodontis adult worm extract (LsAg) affects atherosclerosis in apolipoprotein E–deficient (ApoE−/−) mice. Injections of 50 µg LsAg, i.p. into ApoE−/− mice induced a type 2 immune response shown by increased frequencies of peritoneal eosinophils and alternatively activated macrophages. To analyze the effect of LsAg on atherosclerosis initiation, ApoE−/− mice received a high‐fat diet for 12 wk and weekly injections of 50 µg LsAg from wk 5 to 12. Therapeutic effects on advanced atherosclerosis were analyzed in mice that were fed a high‐fat diet for 12 wk followed by 12 wk of normal chow and weekly LsAg injections. Both preventive and therapeutic LsAg application significantly decreased plaque size. Therapeutic treatment even caused regression of plaque size and macrophage density in the aortic root and reduced Th1‐specific gene expression and intraplaque inflammation. In addition, plaque size after therapeutic treatment was inversely correlated with plaque‐infiltrated alternatively activated macrophages. In vitro, LsAg treatment of HUVECs reduced intracellular levels of phosphorylated NF‐κB‐p65, IκB‐α, and JNK1/2. In bifurcation flow‐through slides, THP‐1 cell adhesion to a HUVEC monolayer was decreased by LsAg in regions of nonuniform shear stress. Applying inhibitors of the respective kinases suggests JNK1/2 inhibition is involved in the suppressed cell adhesion. A switch to an enhanced type 2 immune response by LsAg exerts antiatherogenic effects on murine plaque development, indicating a protective role of a hampered type 1 polarization. In vitro, LsAg affects endothelial signaling pathways, among which JNK1/2 inhibition seems to be involved in the suppression of monocytic cell adhesion under proatherogenic shear stress.—Constanze, K., Tauchi, M., Furtmair, R., Urschel, K., Raaz‐Schrauder, D., Neumann, A.‐L., Frohberger, S. J., Hoerauf, A., Regus, S., Lang, W., Sagban, T. A., Stumpfe, F. M., Achenbach, S., Hübner, M. P., Dietel, B. Filarial extract of Litomosoides sigmodontis induces a type 2 immune response and attenuates plaque development in hyperlipidemic ApoE‐knockout mice. FASEB J. 33, 6497–6513 (2019). http://www.fasebj.org

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Filarial Infection or Antigen Administration Improves Glucose Tolerance in Diet-Induced Obese Mice

Cited by 61 publications

References 54 publications

Contributions of innate type 2 inflammation to adipose function

Contributions of innate type 2 inflammation to adipose function

The effect of three‐monthly albendazole treatment on Th2 responses: Differential effects on IgE and IL‐5

Filarial extract ofLitomosoides sigmodontisinduces a type 2 immune response and attenuates plaque development in hyperlipidemic ApoE‐knockout mice

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