Fc-dependent polyclonal antibodies and antibodies to outer membrane proteins A and B, but not to lipopolysaccharide, protect SCID mice against fatal Rickettsia conorii infection
Fc-dependent polyclonal antibodies and antibodies to outer membrane proteins A and B, but not to lipopolysaccharide, protect SCID mice against fatal Rickettsia conorii infection
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DOI：
10.1128/iai.72.4.2222-2228.2004
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发表时间：
2004-04-01
影响因子：
3.1
通讯作者：
Walker, DH
中科院分区：
文献类型：
--
作者：
Feng, HM;Whitworth, T;Walker, DH
对立克次体的细胞免疫的强调导致了对抗体作用分析的忽视。斑点热立克次体病的优良小鼠模型的可用性使得能够研究抗体在对康氏立克次体的免疫中的潜在作用。将抗立克次体外膜蛋白A（OmpA）、OmpB或脂多糖（LPS）的单克隆抗体、多克隆抗R. Conorii血清、多克隆抗血清的Fab片段或无抗体，48 h后用10 - 50%致死剂量（LD_（50））的R.科诺里。所有接受抗OmpA单克隆抗体的小鼠和四只接受抗OmpB单克隆抗体或多克隆抗血清的小鼠中的两只完全受到保护，但抗LPS抗体或Fab片段的受体没有受到保护。用多克隆抗体处理已感染10 LD 50的R.提前4或5天接种Conorii可使感染小鼠的寿命从10.4天延长至22.5天，并导致24和48小时后脾脏和肝脏中感染性立克次体水平降低。用保护性抗体处理导致R.脾巨噬细胞中的Conorii抗原和吞噬内溶酶体立克次体的死亡和消化。本文还研究了红细胞内抗红细胞单克隆抗体产生的动力学。通过免疫印迹测定的conorii在第6天显示出抗LPS的抗体，在第12天显示出抗OmpA和OmpB的抗体，此时已经从感染中恢复。针对OmpA和OmpB的特定表位的抗体可以保护免受再感染，但它们可能在针对原发感染的免疫中不起关键作用。抗体可能对治疗耐药微生物的感染有用，一些B细胞表位应该包括在亚单位疫苗中。
An emphasis on cellular immunity against Rickettsia has led to neglect of analysis of the role of antibody. The availability of an excellent mouse model of spotted fever rickettsiosis enabled investigation of a potential role of antibody in immunity to Rickettsia conorii. C3H severe combined immunodeficiency (SCID) mice were passively transfused with monoclonal antibodies against rickettsial outer membrane protein A (OmpA), OmpB, or lipopolysaccharide (LPS), polyclonal anti-R. conorii serum, Fab fragments of polyclonal antiserum, or no antibodies and then challenged 48 h later with 10 50% lethal doses (LD50) of R. conorii. All mice that received monoclonal antibodies against OmpA and two of four mice that received monoclonal antibodies against OmpB or polyclonal antisera were completely protected, but the recipients of anti-LPS antibodies or the Fab fragments were not protected. Polyclonal antibody treatment of C3H SCID mice that had been infected with 10 LD50 of R. conorii 4 or 5 days earlier prolonged the life of the infected mice from 10.4 to 22.5 days and resulted in decreased levels of infectious rickettsiae in the spleen and liver 24 and 48 h later. Treatment with protective antibodies resulted in the development of large aggregates of R. conorii antigens in splenic macrophages and intraphagolysosomal rickettsial death and digestion. The kinetics of development of antibodies to R. conorii determined by immunoblotting revealed antibodies to LPS on day 6 and antibodies to OmpA and OmpB on day 12, when recovery from the infection had already occurred. Antibodies to particular epitopes of OmpA and OmpB may protect against reinfection, but they may not play a key role in immunity against primary infection. Antibodies might be useful for treating infections with antibiotic-resistant organisms, and some B-cell epitopes should be included in a subunit vaccine.