Converso T R, Goulart C, Rodriguez D, Darrieux M, Leite L C C
Centro de Biotecnologia, Instituto Butantan, São Paulo, Brazil; Programa de Pós Graduação Interunidades em Biotecnologia USP-IPT-IB, São Paulo, Brazil.
Centro de Biotecnologia, Instituto Butantan, São Paulo, Brazil.
Vaccine. 2017 Jan 3;35(1):149-155. doi: 10.1016/j.vaccine.2016.11.027. Epub 2016 Nov 21.
Streptococcus pneumoniae (pneumococcus) is a human pathogen that can cause otitis media, pneumonia and, in severe cases, meningitis and bacteremia. The pneumococcus expresses PotD, a protein belonging to the polyamines transporter complex called PotABCD. PotD is a membrane-associated protein that binds polyamines and has been shown to be important for virulence. In this work we demonstrate that subcutaneous immunization with rPotD reduces the bacterial load in the nasal tissue of mice, following intranasal challenge with a type 6B pneumococcus. The protective effect correlated with the induction of high levels of antibodies in the immunized group; the antibodies were able to increase bacterial phagocytosis by mouse peritoneal cells. The cellular immune response was characterized by the production of gamma-interferon, IL-2 and IL-17 by splenocytes and nitric oxide by peritoneal cells of immunized mice, upon stimulation with rPotD. Taken together our results suggest that PotD is a promising candidate to be included in a protein based pneumococcal vaccine, able to induce phagocytic antibodies, a Th1 cellular immune response and production of IL-17, reducing nasopharyngeal colonization, the main event responsible for transmission of pneumococci in humans.
肺炎链球菌（肺炎球菌）是一种人类病原体，可导致中耳炎、肺炎，严重时可引发脑膜炎和菌血症。肺炎球菌表达PotD，这是一种属于名为PotABCD的多胺转运复合物的蛋白质。PotD是一种与膜相关的蛋白质，可结合多胺，并且已被证明对毒力很重要。在这项研究中，我们证明，用重组PotD进行皮下免疫可降低小鼠鼻腔组织中的细菌载量，前提是在鼻腔内用6B型肺炎球菌进行攻击。保护作用与免疫组中高水平抗体的诱导相关；这些抗体能够增加小鼠腹膜细胞对细菌的吞噬作用。细胞免疫反应的特征是，在重组PotD刺激后，免疫小鼠的脾细胞产生γ干扰素、白细胞介素-2和白细胞介素-17，腹膜细胞产生一氧化氮。综合我们的结果表明，PotD是一种很有前景的候选物质，可纳入基于蛋白质的肺炎球菌疫苗中，能够诱导吞噬性抗体、Th1细胞免疫反应和白细胞介素-17的产生，减少鼻咽部定植，这是肺炎球菌在人类中传播的主要环节。
