Filarial extract of Litomosoides sigmodontis induces a type 2 immune response and attenuates plaque development in hyperlipidemic ApoE-knockout mice

Journal article


Publication Details

Author(s): Kühn C, Tauchi M, Furtmair R, Urschel K, Raaz-Schrauder D, Neumann AL, Frohberger SJ, Hoerauf A, Regus S, Lang W, Sagban TA, Stumpfe FM, Achenbach S, Hübner MP, Dietel B
Journal: The FASEB Journal
Publication year: 2019
Volume: 33
Journal issue: 5
Pages range: 6497-6513
ISSN: 0892-6638
eISSN: 1530-6860


Abstract

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.


FAU Authors / FAU Editors

Achenbach, Stephan Prof. Dr. med.
Medizinische Klinik 2 - Kardiologie, Angiologie
Dietel, Barbara
Graduiertenzentrum der FAU
Furtmair, Roman
Lehrstuhl für Innere Medizin II
Kühn, Constanze
Medizinische Klinik 2 - Kardiologie, Angiologie
Lang, Werner apl. Prof. Dr.
Gefäßchirurgische Abteilung
Raaz-Schrauder, Dorette PD Dr.
Medizinische Fakultät
Regus, Susanne PD Dr.
Gefäßchirurgische Abteilung
Urschel, Katharina
Graduiertenzentrum der FAU


External institutions with authors

Universitätsklinikum Bonn


How to cite

APA:
Kühn, C., Tauchi, M., Furtmair, R., Urschel, K., Raaz-Schrauder, D., Neumann, A.L.,... Dietel, B. (2019). Filarial extract of Litomosoides sigmodontis induces a type 2 immune response and attenuates plaque development in hyperlipidemic ApoE-knockout mice. The FASEB Journal, 33(5), 6497-6513. https://dx.doi.org/10.1096/fj.201800947RR

MLA:
Kühn, Constanze, et al. "Filarial extract of Litomosoides sigmodontis induces a type 2 immune response and attenuates plaque development in hyperlipidemic ApoE-knockout mice." The FASEB Journal 33.5 (2019): 6497-6513.

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Last updated on 2019-10-09 at 09:33