STUDIES OF GROUP-B STREPTOCOCCAL INFECTION IN MICE DEFICIENT IN COMPLEMENT COMPONENT C3 OR C4 DEMONSTRATE AN ESSENTIAL ROLE FOR COMPLEMENT IN BOTH INNATE AND ACQUIRED-IMMUNITY
STUDIES OF GROUP-B STREPTOCOCCAL INFECTION IN MICE DEFICIENT IN COMPLEMENT COMPONENT C3 OR C4 DEMONSTRATE AN ESSENTIAL ROLE FOR COMPLEMENT IN BOTH INNATE AND ACQUIRED-IMMUNITY
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DOI：
10.1073/pnas.92.25.11490
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发表时间：
1995-12-05
影响因子：
11.1
通讯作者：
CARROLL, MC
中科院分区：
文献类型：
--
作者：
WESSELS, MR;BUTKO, P;CARROLL, MC
B族链球菌（GBS）可引起新生儿败血症和脑膜炎，也可引起成年人严重感染。特异性抗体是新生儿保护性免疫的重要因素，但血清补体的作用尚不明确。我们已经使用胚胎干细胞中的基因靶向方法来产生完全缺乏补体成分C3的小鼠，C3缺陷小鼠与补体成分C4缺陷小鼠的比较表明，50%的C3缺陷小鼠的补体成分C4缺陷小鼠的补体成分C3缺陷小鼠的补体成分C4缺陷小鼠的补体成分与对照小鼠相比，GBS感染的致死剂量分别降低了约50倍和25倍，在特异性抗体和C4缺陷血清存在下，GBS在体外被人血白细胞有效地杀死，但不存在C3缺陷血清，体内研究证实了体外C3缺陷型血清的缺陷调理作用，其中用特异性抗体被动免疫妊娠母鼠可保护正常和C4缺陷型幼鼠免受GBS攻击，但不能保护C3缺陷型幼鼠，这些结果表明，在特异性抗体存在下，旁路途径足以介导有效的调理吞噬作用和对GBS的保护性免疫。缺乏C3或C4的非免疫小鼠对感染的易感性增加，这意味着经典途径在宿主防御GBS感染中起重要作用，缺乏特异性免疫力。
Group B streptococci (GBS) cause sepsis and meningitis in neonates and serious infections in adults with underlying chronic illnesses, Specific antibodies have been shown to be an important factor in protective immunity for neonates, but the role of serum complement is less web defined, To elucidate the function of the complement system in immunity to this pathogen, we have used the approach of gene targeting in embryonic stem cells to generate mice totally deficient in complement component C3, Comparison of C3-deficient mice with mice deficient in complement component C4 demonstrated that the 50% lethal dose for GBS infection was reduced by approximate to 50-fold and 25-fold, respectively, compared to control mice, GBS were effectively killed in vitro by human blood leukocytes in the presence of specific antibody and C4-deficient serum but not C3-deficient serum, The defective opsonization by C3 deficient serum in vitro was corroborated by in vivo studies in which passive immunization of pregnant dams with specific antibodies conferred protection from GBS challenge to normal and C4-deficient pups but not C3-deficient pups, These results indicate that the alternative pathway is sufficient to mediate effective opsonophagocytosis and protective immunity to GBS in the presence of specific antibody, In contrast, the increased susceptibility to infection of nonimmune mice deficient in either C3 or C4 implies that the classical pathway plays an essential role in host defense against GBS infection in the absence of specific immunity.