Scaringi L, Tissi L, Cornacchione P, Rosati E, Campanelli C, von Hunolstein C, Orefici G, Rossi R, Marconi P
Department of Clinical Medicine, Pathology and Pharmacology, University of Perugia, Italy.
FEMS Immunol Med Microbiol. 1994 Aug;9(2):151-62. doi: 10.1111/j.1574-695X.1994.tb00486.x.
There is ample evidence that protection against group B streptococcal (GBS) disease, both in experimental animals and in humans, is related to the presence of specific antibodies and complement. However, until now the possibility of increasing resistance to GBS infection by potentiating natural cell-mediated immunity in the host, has not been explored. In this study we examine the effect of administering in vivo MVE-2 (a polymer fraction of 1,2-co-polymer of divinyl ether and maleic anhydride) and inactivated Candida albicans (CA) cells on mouse resistance to the reference strain type Ia 090 GBS (GBS-090) lethal infection. MVE-2 and CA, respectively a synthetic and a microbial biological response modifier (BRM), are strong inducers and activators of natural resistance effectors, such as natural killer (NK) cells, macrophages and polymorphonuclear cells (PMN). The results showed that MVE-2 protected 100% CD-1 mice from a systemic lethal challenge with GBS-090 (5 x 10(3) microorganisms/mouse) when administered 3 days before infection at dose of 50 mg kg-1. CA treatment, in five doses (CA-5d) over 14 days protected 100% mice when administered at 2 x 10(7) cells/mouse and when the last CA injection was given 1 day before the GBS-090 challenge. Instead, when the GBS-090 challenge was performed by intraperitoneal route, protection was obtained with CA-5d treatment but not with MVE-2. The possibility that MVE-2 or CA stimulated a rapid production of specific antibodies against GBS-090 infection was excluded by the ELISA assay. Evidence exists that NK cells do not play a primary role as effectors in the MVE-2 and CA conferred protection since the strong reduction in NK activity, due to in vivo administration of anti-asialo GM1 antibodies before GBS-090 infection, did not influence the BRM-induced protection. Besides, high NK activity levels, induced by in vivo rhIL-2 administration, did not protect the mice against GBS-090 infection. Both studies on in vivo clearance and in vitro microbicidal activity, showed that, after 1 h, immunopotentiated effectors were unable to kill GBS-090, but were highly effective against GBS type VI. These results seem to indicate that intracellular GBS-090 killing is a slow process requiring more than 1 h. This study demonstrates that it is possible to increase resistance to GBS-090 lethal infection by BRMs, by potentiating the antibody-independent microbicidal activity of the phagocytes.
有充分证据表明，在实验动物和人类中，针对B族链球菌（GBS）疾病的保护作用与特定抗体和补体的存在有关。然而，到目前为止，尚未探索通过增强宿主天然细胞介导的免疫来提高对GBS感染抵抗力的可能性。在本研究中，我们研究了体内给予MVE - 2（二乙烯基醚与马来酸酐的1,2 - 共聚物的聚合物级分）和灭活白色念珠菌（CA）细胞对小鼠抵抗参考菌株Ia型090 GBS（GBS - 090）致死性感染的影响。MVE - 2和CA分别是一种合成的和微生物的生物反应调节剂（BRM），是天然抗性效应器（如自然杀伤（NK）细胞、巨噬细胞和多形核细胞（PMN））的强诱导剂和激活剂。结果表明，当在感染前3天以50 mg/kg的剂量给予时，MVE - 2可保护100%的CD - 1小鼠免受GBS - 090（5×10³个微生物/小鼠）的全身致死性攻击。CA处理，在14天内分五剂（CA - 5d）给予，当以2×10⁷个细胞/小鼠给药且最后一次CA注射在GBS - 090攻击前1天进行时，可保护100%的小鼠。相反，当通过腹腔途径进行GBS - 090攻击时，CA - 5d处理可获得保护，但MVE - 2则不能。ELISA检测排除了MVE - 2或CA刺激针对GBS - 090感染快速产生特异性抗体的可能性。有证据表明，NK细胞在MVE - 2和CA赋予的保护中并非作为主要效应器发挥作用，因为在GBS - 090感染前体内给予抗唾液酸GM1抗体导致NK活性大幅降低，但并未影响BRM诱导的保护作用。此外，体内给予rhIL - 2诱导的高NK活性水平并不能保护小鼠免受GBS - 090感染。体内清除和体外杀菌活性的研究均表明，1小时后，免疫增强的效应器无法杀死GBS - 090，但对VI型GBS具有高效杀伤力。这些结果似乎表明，细胞内GBS - 090的杀伤是一个缓慢的过程，需要超过1小时。本研究表明，通过生物反应调节剂增强吞噬细胞的非抗体依赖性杀菌活性，可以提高对GBS - 090致死性感染的抵抗力。
