Interleukin-15 Complex Treatment Protects Mice from Cerebral Malaria by Inducing Interleukin-10-Producing Natural Killer Cells

被引：60

作者：

Burrack, Kristina S. ^{[1
]}

Huggins, Matthew A. ^{[1
,2
]}

Taras, Emily ^{[3
]}

Dougherty, Philip ^{[3
]}

Henzler, Christine M. ^{[4
]}

Yang, Rendong ^{[4
]}

Alter, Sarah ^{[5
]}

Jeng, Emily K. ^{[5
]}

Wong, Hing C. ^{[5
]}

Felices, Martin ^{[3
]}

Cichocki, Frank ^{[3
]}

Miller, Jeffrey S. ^{[3
]}

Hart, Geoffrey T. ^{[6
]}

Johnson, Aaron J. ^{[2
]}

Jameson, Stephen C. ^{[1
]}

Hamilton, Sara E. ^{[1
]}

机构：

[1] Univ Minnesota, Ctr Immunol, Dept Lab Med & Pathol, Minneapolis, MN 55414 USA

[2] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA

[3] Univ Minnesota, Dept Med, Minneapolis, MN 55414 USA

[4] Univ Minnesota, Supercomp Inst Adv Computat Res, Minneapolis, MN 55414 USA

[5] Altor BioSci Corp, Miramar, FL 33025 USA

[6] Univ Minnesota, Ctr Immunol, Dept Med, Minneapolis, MN 55414 USA

来源：

IMMUNITY | 2018年 / 48卷 / 04期

关键词：

CD8(+) T-CELLS; NK CELLS; IN-VIVO; IL-10; PRODUCTION; FUSION COMPLEX; BRAIN; SUPERAGONIST; PATHOGENESIS; RESPONSES; ANTIBODY;

D O I：

10.1016/j.immuni.2018.03.012

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Cerebral malaria is a deadly complication of Plasmodium infection and involves blood brain barrier (BBB) disruption following infiltration of white blood cells. During experimental cerebral malaria (ECM), mice inoculated with Plasmodium berghei ANKA-infected red blood cells develop a fatal CM-like disease caused by CD8(+) T cell-mediated pathology. We found that treatment with interleukin-15 complex (IL-15C) prevented ECM, whereas IL-2C treatment had no effect. IL-15C-expanded natural killer (NK) cells were necessary and sufficient for protection against ECM. IL-15C treatment also decreased CD8(+) T cell activation in the brain and prevented BBB breakdown without influencing parasite load. IL-15C induced NK cells to express IL-10, which was required for IL-15C-mediated protection against ECM. Finally, we show that ALT-803, a modified human IL-15C, mediates similar induction of IL-10 in NK cells and protection against ECM. These data identify a regulatory role for cytokine-stimulated NK cells in the prevention of a pathogenic immune response.

引用

页码：760 / +

页数：17

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