Active and passive intranasal immunizations with streptococcal surface protein C5a peptidase prevent infection of murine nasal mucosa-associated lymphoid tissue, a functional homologue of human tonsils
Active and passive intranasal immunizations with streptococcal surface protein C5a peptidase prevent infection of murine nasal mucosa-associated lymphoid tissue, a functional homologue of human tonsils
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DOI：
10.1128/iai.73.12.7878-7886.2005
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发表时间：
2005-12-01
影响因子：
3.1
通讯作者：
Cleary, PP
中科院分区：
文献类型：
--
作者：
Park, HS;Cleary, PP
C5a肽酶又称SCPA(Surface-Bound C5a Peptidase)，是A组链球菌(GAS)的表面结合蛋白，是多种人类疾病的病原体，包括咽炎、脓疱病、中毒性休克、坏死性筋膜炎以及感染后的后遗症风湿热和风湿性心脏病。这种蛋白在不同的血清型中高度保守，也在B、C和G群链球菌的人类分离株中表达。人类扁桃体是气体的主要储存库，在全球范围内维持着地方性疾病。我们最近报道，GAS优先靶向小鼠的鼻黏膜相关淋巴组织(NALT)，这是一种功能类似于人类扁桃体的组织。使用C5a多肽酶功能缺失突变体和鼻腔感染模型的实验表明，这种蛋白酶是有效定植NALT所必需的。一种有效的疫苗应该可以预防这种次级淋巴组织的感染；因此，我们研究了抗SCPA抗体预防NALT链球菌感染的可能性。实验表明，重组SCPA蛋白单独或联合霍乱毒素鼻腔免疫小鼠后，NALT的GAS定植显著减少，而仅用磷酸盐缓冲生理盐水免疫的对照小鼠则观察到高度的GAS定植。此外，经鼻腔给药的抗SCPA血清可保护小鼠免受链球菌感染。这些结果表明，鼻腔免疫SCPA将防止人类扁桃体的定植和感染，从而消除保持地方性疾病的潜在宿主。
C5a peptidase, also called SCPA (surface-bound C5a peptidase), is a surface-bound protein on group A streptococci (GAS), etiologic agents for a variety of human diseases including pharyngitis, impetigo, toxic shock, and necrotizing fasciitis, as well as the postinfection sequelae rheumatic fever and rheumatic heart disease. This protein is highly conserved among different serotypes and is also expressed in human isolates of group B, C, and G streptococci. Human tonsils are the primary reservoirs for GAS, maintaining endemic disease across the globe. We recently reported that GAS preferentially target nasal mucosa-associated lymphoid tissue (NALT) in mice, a tissue functionally analogous to human tonsils. Experiments using a C5a peptidase loss-of-function mutant and an intranasal infection model showed that this protease is required for efficient colonization of NALT. An effective vaccine should prevent infection of this secondary lymphoid tissue; therefore, the potential of anti-SCPA antibodies to protect against streptococcal infection of NALT was investigated. Experiments showed that GAS colonization of NALT was significantly reduced following intranasal immunization of mice with recombinant SCPA protein administered alone or with cholera toxin, whereas a high degree of GAS colonization of NALT was observed in control mice immunized with phosphate-buffered saline only. Moreover, administration of anti-SCPA serum by the intranasal route protected mice against streptococcal infection. These results suggest that intranasal immunization with SCPA would prevent colonization and infection of human tonsils, thereby eliminating potential reservoirs that maintain endemic disease.