Kotsyfakis Michalis, Anderson Jennifer M, Andersen John F, Calvo Eric, Francischetti Ivo M B, Mather Thomas N, Valenzuela Jesus G, Ribeiro José M C
Vector Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
J Immunol. 2008 Oct 15;181(8):5209-12. doi: 10.4049/jimmunol.181.8.5209.
Ixodes scapularis ticks transmit the Lyme disease agent in the United States. Although strong antitick immunity mediates tick rejection by certain vertebrates, only a few Ags have been molecularly characterized. We show that guinea pig vaccination against a secreted tick salivary immunomodulator, sialostatin L2, can lead to decreased feeding ability of I. scapularis nymphs. Increased rejection rate, prolonged feeding time, and apparent signs of inflammation were observed for nymphs attached to vaccinated animals, indicating a protective host immune response. Interestingly, sialostatin L2 humoral recognition does not take place upon repeated tick exposure in control animals, but only in the vaccinated animals that neutralize sialostatin L2 action. Therefore, we demonstrate an essential sialostatin L2 role upon nymphal infestation that can be blocked by vertebrate immunity and propose the discovery of similarly "silent" Ags toward the development of a multicomponent vaccine that will protect against tick bites and the pathogens they transmit.
肩突硬蜱在美国传播莱姆病病原体。尽管强大的抗蜱免疫介导某些脊椎动物排斥蜱虫,但仅有少数抗原得到了分子特征描述。我们发现,豚鼠接种针对一种分泌型蜱唾液免疫调节剂——唾液抑制素L2的疫苗后,肩突硬蜱若虫的取食能力会下降。附着在接种疫苗动物身上的若虫出现排斥率增加、取食时间延长以及明显的炎症迹象,表明宿主产生了保护性免疫反应。有趣的是,在对照动物中,反复接触蜱虫时不会出现对唾液抑制素L2的体液识别,而仅在中和了唾液抑制素L2作用的接种疫苗动物中出现。因此,我们证明了唾液抑制素L2在若虫侵染时的关键作用,这种作用可被脊椎动物免疫阻断,并提议针对开发一种多组分疫苗来预防蜱虫叮咬及其传播的病原体,发现类似的“沉默”抗原。