Rogers H W, Unanue E R
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Infect Immun. 1993 Dec;61(12):5090-6. doi: 10.1128/iai.61.12.5090-5096.1993.
The importance of neutrophils in killing extracellular, pyogenic bacteria has long been established. However, there is only indirect evidence for a role for neutrophils in resistance against intracellular organisms. In this study, we directly demonstrate the involvement of neutrophils in defense against Listeria monocytogenes in normal C.B-17 immunocompetent and C.B-17 SCID mice. Because of the lack of sterilizing T-cell immunity, SCID mice are unable to completely eliminate listeriae systemically and become chronically infected. Both immunocompetent and SCID mice treated with a specific neutrophil-depleting monoclonal antibody during the early stages of Listeria infection were rendered remarkably sensitive to the organism, with a high level of mortality resulting from enhanced bacterial growth. At a late stage of infection in SCID mice, however, administration of neutrophil-depleting antibody did not affect mortality. In spite of the neutrophil depletion, other parameters of nonspecific immune function were normal. Macrophage infiltration to the site of infection and macrophage expression of major histocompatibility complex class II molecules were unaffected. Moreover, NK cell functions were normal as measured by infiltration to an infection site and gamma interferon production. These data demonstrate an important role for neutrophils in controlling the acute phase of Listeria infection, cooperating with, and yet independent of, macrophages and NK cells.
中性粒细胞在杀灭细胞外化脓性细菌方面的重要性早已得到证实。然而,关于中性粒细胞在抵抗细胞内病原体方面发挥作用的证据仅为间接证据。在本研究中,我们直接证明了在正常的C.B-17免疫 competent 和C.B-17 SCID小鼠中,中性粒细胞参与了对单核细胞增生李斯特菌的防御。由于缺乏杀菌性T细胞免疫,SCID小鼠无法全身彻底清除李斯特菌,并会发生慢性感染。在李斯特菌感染早期,用特异性中性粒细胞耗竭单克隆抗体处理的免疫 competent 和SCID小鼠,对该病原体均表现出显著的敏感性,细菌生长增强导致高死亡率。然而,在SCID小鼠感染后期,给予中性粒细胞耗竭抗体并不影响死亡率。尽管中性粒细胞减少,但非特异性免疫功能的其他参数正常。巨噬细胞向感染部位的浸润以及主要组织相容性复合体II类分子的巨噬细胞表达均未受影响。此外,通过向感染部位浸润和γ干扰素产生来衡量,NK细胞功能正常。这些数据证明了中性粒细胞在控制李斯特菌感染急性期方面的重要作用,它与巨噬细胞和NK细胞协同作用,但又独立于它们。