Fernandez Stefan, Cisney Emily D, Hall Shannan I, Ulrich Robert G
United States Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Frederick, MD 21702, USA.
Clin Vaccine Immunol. 2011 Apr;18(4):667-75. doi: 10.1128/CVI.00477-10. Epub 2011 Feb 16.
The nasopharynx-associated lymphoid tissue (NALT) of humans and other mammals is associated with immunity against airborne infections, though it is generally considered to be a secondary component of the mucosa-associated lymphoid system. We found that protective immunity to a virulence factor of nasal mucosa-colonizing Staphylococcus aureus, staphylococcal enterotoxin B (SEB), requires a functional NALT. We examined the role of NALT using intranasal (IN) vaccination with a recombinant SEB vaccine (rSEBv) combined with an adjuvant in a mouse model of SEB-induced toxic shock. The rSEBv was rapidly internalized by NALT cells at the mucosal barrier, and transport into NALT was accelerated by inclusion of a Toll-like receptor 4 (TLR4) agonist. Vaccine-induced germinal centers of B cells formed within NALT, accompanied by elevated levels of IgA(+) and IgG(+) cells, and these were further increased by TLR4 activation. The NALT was the site of specific anti-rSEBv IgA and IgG production but was also influenced by intraperitoneal (IP) inoculation and perhaps other isolated lymphoid follicles observed within the nasal cavity. Vaccination by the IN route generated robust levels of anti-rSEBv IgA in saliva, nasal secretions, and blood compared to much lower levels after IP vaccination. IN vaccination also induced secretion of anti-rSEBv IgG in the blood and nasal secretions. Significantly, the efficacy of IN vaccination was dependent on NALT, as surgical removal resulted in greater sensitivity to IN challenge with wild-type SEB. Thus, protective immunity to SEB within the nasal sinuses was elicited by responses originating in NALT.
人类和其他哺乳动物的鼻咽相关淋巴组织（NALT）与抵抗空气传播感染的免疫相关，尽管它通常被认为是黏膜相关淋巴系统的次要组成部分。我们发现，对鼻腔黏膜定植的金黄色葡萄球菌的一种毒力因子——葡萄球菌肠毒素B（SEB）的保护性免疫需要功能性的NALT。我们在SEB诱导的中毒性休克小鼠模型中，使用重组SEB疫苗（rSEBv）与佐剂联合经鼻内（IN）接种来研究NALT的作用。rSEBv在黏膜屏障处被NALT细胞迅速内化，并且通过包含Toll样受体4（TLR4）激动剂可加速其向NALT的转运。疫苗诱导的B细胞生发中心在NALT内形成，同时伴有IgA(+)和IgG(+)细胞水平升高，并且这些细胞水平通过TLR4激活进一步增加。NALT是特异性抗rSEBv IgA和IgG产生的部位，但也受到腹腔内（IP）接种以及鼻腔内观察到的其他孤立淋巴滤泡的影响。与IP接种后低得多的水平相比，经IN途径接种在唾液、鼻腔分泌物和血液中产生了高水平的抗rSEBv IgA。IN接种还诱导血液和鼻腔分泌物中抗rSEBv IgG的分泌。重要的是，IN接种的效果依赖于NALT，因为手术切除导致对野生型SEB经IN攻击的敏感性增加。因此，鼻窦内对SEB的保护性免疫是由源自NALT的反应引发的。
