IL-23 Is Required for Protection against Systemic Infection with Listeria monocytogenes

被引:85
作者
Meeks, Karen D. [1 ]
Sieve, Amy N. [1 ]
Kolls, Jay K. [2 ]
Ghilardi, Nico [3 ]
Berg, Rance E. [1 ]
机构
[1] Univ N Texas Hlth Sci Ctr, Dept Mol Biol & Immunol, Ft Worth, TX 76107 USA
[2] Louisiana State Univ, Hlth Sci Ctr, Dept Genet & Pediat, New Orleans, LA 70112 USA
[3] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA
基金
美国国家卫生研究院;
关键词
COLONY-STIMULATING FACTOR; INNATE IMMUNE PROTECTION; MUCOSAL HOST-DEFENSE; T-CELL-ACTIVATION; MONOCLONAL-ANTIBODY; INTERLEUKIN-6-DEFICIENT MICE; ADAPTIVE IMMUNITY; INTERFERON-GAMMA; TH17; CELLS; RESPONSES;
D O I
10.4049/jimmunol.0901588
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Listeria monocytogenes (LM) is a Gram-positive, intracellular bacterium that can induce spontaneous abortion, septicemia, and meningitis. Although it is known that neutrophils are required for elimination of the bacteria and for survival of the host, the mechanisms governing the recruitment of neutrophils to LM-infected tissues are not fully understood. We demonstrate here that IL-23 and the IL-17 receptor A (IL-17RA), which mediates both IL-17A and IL-17F signaling, are necessary for resistance against systemic LM infection. LM-infected IL-23p19 knockout (KO) mice have decreased production of IL-17A and IL-17F, while IFN-gamma production is not altered by the lack of IL-23. LM induces the production of IL-17A from gamma delta T cells, but not CD4, CD8, or INK cells. Furthermore, a lack of efficient neutrophil recruitment to the liver is evident in both IL-23p19 KO and IL-17RA KO mice during LM infection. Immunocytochemical analysis of infected livers revealed that neutrophils were able to localize with LM in IL-23p19 KO and IL-17RA KO mice, indicating that IL-23 and IL-17RA do not regulate the precise localization of neutrophils with LM. The importance of IL-23-induced IL-17A was demonstrated by injecting IL-23p19 KO mice with recombinant IL-17A. These mice had reduced LM bacterial burdens compared with IL-23p19 KO mice that did not receive IL-17A. These results indicate that during LM infection, IL-23 regulates the production of IL-17A and IL-17F from gamma delta T cells, resulting in optimal liver neutrophil recruitment and enhanced bacterial clearance. The Journal of Immunology, 2009, 183: 8026-8034.
引用
收藏
页码:8026 / 8034
页数:9
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