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针对小鼠上生殖道疾病的保护性免疫与气道中复制的衣原体诱导的高 IFNγ但低 IL-17 T 细胞和抗分泌蛋白抗体反应相关。

Protective immunity against mouse upper genital tract pathology correlates with high IFNγ but low IL-17 T cell and anti-secretion protein antibody responses induced by replicating chlamydial organisms in the airway.

机构信息

Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.

出版信息

Vaccine. 2012 Jan 5;30(2):475-85. doi: 10.1016/j.vaccine.2011.10.059. Epub 2011 Nov 10.

Abstract

To search for optimal immunization conditions for inducing protective immunity against upper genital tract pathologies caused by chlamydial intravaginal infection, we compared protection efficacy in mice immunized intranasally or intramuscularly with live or inactivated Chlamydia muridarum organisms. Mice immunized intranasally with live organisms developed strong protection against both vaginal shedding of infectious organisms and upper genital tract pathologies. The protection correlated with a robust antigen-specific T cell response with high IFNγ but low IL-17. Although a significant level of IL-5 was also detected, these mice maintained an overall Th1-dorminant immunity following immunization and challenge infection. On the contrary, mice immunized intranasally with inactivated organisms or intramuscularly with live or inactivated organisms produced high levels of IL-17 and still developed significant upper genital tract pathologies. High titers of antibodies against chlamydial secretion antigens were detected only in mice immunized intranasally with live organisms but not mice in other groups, suggesting that the intranasally inoculated live organisms were able to undergo replication and immune responses to the chlamydial secretion proteins may contribute to protective immunity. These observations have provided important information on how to develop subunit vaccines for inducing protective immunity against urogenital infection with Chlamydia trachomatis organisms.

摘要

为了寻找诱导针对衣原体阴道感染引起的上生殖道疾病的保护性免疫的最佳免疫条件,我们比较了经鼻腔或肌肉内接种活或灭活的鼠衣原体生物体对小鼠的保护效果。经鼻腔接种活生物体的小鼠对阴道分泌物中传染性生物体和上生殖道疾病均具有强烈的保护作用。这种保护与强烈的抗原特异性 T 细胞反应相关,该反应具有高 IFNγ但低 IL-17。尽管也检测到相当水平的 IL-5,但这些小鼠在免疫和挑战感染后仍保持总体 Th1 优势免疫。相反,经鼻腔接种灭活生物体或肌肉内接种活或灭活生物体的小鼠产生高水平的 IL-17,并且仍然发生显著的上生殖道疾病。仅在经鼻腔接种活生物体的小鼠中检测到针对衣原体分泌抗原的高滴度抗体,而其他组的小鼠则没有,这表明鼻腔接种的活生物体能够进行复制,并且对衣原体分泌蛋白的免疫反应可能有助于保护性免疫。这些观察结果为如何开发针对沙眼衣原体生物体引起的泌尿生殖道感染的亚单位疫苗提供了重要信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c29/3246108/2c20d856a5b0/nihms337141f1.jpg

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