Targeting IL-27 and/or IL-10 in Experimental Murine Visceral Leishmaniasis

被引:4
|
作者
Murray, Henry W. [1 ]
机构
[1] Well Cornell Med Coll, Dept Med, Div Infect Dis, 1300 York Ave, New York, NY 10065 USA
来源
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE | 2020年 / 103卷 / 05期
关键词
DONOVANI INFECTION; RECEPTOR BLOCKADE; INTERLEUKIN-10; IMMUNITY;
D O I
10.4269/ajtmh.20-0531
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
Interleukin-10 (IL-10) and interleukin-27 (IL-27) both exert counterregulatory immunodeactivation in visceral Leishmania donovani infection. Westudied experimental L. donovani infection in the livers of IL-10(-/-) and IL-27R alpha(-/-) mice and observed that in IL-27R alpha(-/-), but not IL-10(-/-) mice, interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) were required for heightened granulomatous inflammation and accelerated control of intracellular parasite replication. This difference in mechanism, along with residual IL-10 activity in IL-27R alpha(-/-) mice, suggested targeting IL-27 in addition to IL-10 in a macrophage-activating, anti-counterregulatory cytokine treatment strategy. In C57BL/6 wild-type mice with established liver infection, a single injection of anti-IL-27 p28 or anti-IL-10R monoclonal antibody enhanced granuloma assembly, enabled macrophage activation, and induced comparable parasite killing (49-56%). However, anti-IL-27 p28 plus anti-IL-10R combination treatment did not increase leishmanicidal effects. These results suggest that IL-27 and IL-10 may operate in a linked deactivating mechanism and that in this intracellular infection, either IL-27 or IL-10 is a suitable immunotherapeutic target.
引用
收藏
页码:1938 / 1941
页数:4
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