State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin, China.
Microbiol Spectr. 2022 Dec 21;10(6):e0321022. doi: 10.1128/spectrum.03210-22. Epub 2022 Oct 26.
Little is known about the damage to the important peripheral immune organ spleen caused by Streptococcus suis infection. In this study, we found that S. suis induced splenomegaly and lymphocyte disruption in spleens of mice. To explore the mechanism of splenic lesions induced by S. suis, we conducted further studies. The results showed that S. suis induced apoptosis in B cells, which is related to the cleavage of caspase-3 and caspase-8, but not the release of apoptosis-inducing factor (AIF). Thus, S. suis induced apoptosis in the spleen through caspase-dependent and AIF-independent pathways. Inflammation lesions induced in the spleen of infected mice were also investigated; we found macrophages increased in histopathological lesions of infected spleens from 12 h postinoculation to 7 days postinoculation (dpi), and the type of increased macrophages was M1 type by confocal microscopy, which can secrete proinflammatory cytokines. Meanwhile, inflammasome NLRP3 and caspase-1 were activated, and gasdermin D (GSDMD) was cleaved, which causes pyroptosis that may result in the release of numerous proinflammatory cytokines. What's more, the increase of p-JNK and p-p38 indicated that the MAPK pathway was also involved in the proinflammatory responses during S. suis infection, whereas anti-inflammatory responses in spleen were suppressed, with regulatory T cells (Tregs) upregulating at 1 dpi. Taken together, proinflammatory immune responses dominate in early infection, which induce splenomegaly and splenocyte apoptosis. This is the first report of mechanisms associated with S. suis-induced splenic lesions. Streptococcus suis serotype 2 is considered an emerging pathogen and represents a threat to humans and animals. The spleen is an important peripheral immune organ, and splenomegaly is a consequence of lesions and an important clinical indicator of S. suis infection. However, knowledge of the mechanisms underlying spleen lesions is still very limited. In the present work, we made the investigation to explain the phenomenon and the related immunomodulation in a mouse infection model. The obtained results show that inflammation contributes to splenomegaly, while apoptosis contributes to lymphocyte disruption in spleens. Related signaling pathways were discovered which have never been associated with S. suis-induced splenic injury. The new knowledge generated will help us better understand the mechanism of S. suis pathogenesis.
关于猪链球菌感染对重要外周免疫器官脾脏造成的损害知之甚少。在本研究中，我们发现猪链球菌可诱导小鼠脾脏肿大和淋巴细胞破坏。为了探讨猪链球菌引起脾脏损伤的机制，我们进行了进一步的研究。结果表明，猪链球菌诱导 B 细胞凋亡与 caspase-3 和 caspase-8 的裂解有关，但与凋亡诱导因子（AIF）的释放无关。因此，猪链球菌通过 caspase 依赖性和 AIF 非依赖性途径诱导脾脏凋亡。我们还研究了感染小鼠脾脏中炎症损伤；我们发现，从接种后 12 小时到 7 天，感染脾脏的组织病理学损伤中巨噬细胞增加，通过共聚焦显微镜观察到增加的巨噬细胞类型为 M1 型，可分泌促炎细胞因子。同时，NLRP3 炎性小体和 caspase-1 被激活，gasdermin D（GSDMD）被切割，导致可能导致大量促炎细胞因子释放的细胞焦亡。更重要的是，p-JNK 和 p-p38 的增加表明 MAPK 通路也参与了猪链球菌感染过程中的促炎反应，而脾脏中的抗炎反应受到抑制，调节性 T 细胞（Tregs）在 1dpi 时上调。总之，早期感染以促炎免疫反应为主，导致脾脏肿大和脾细胞凋亡。这是首次报道与猪链球菌诱导的脾脏损伤相关的机制。猪链球菌 2 型被认为是一种新兴病原体，对人类和动物构成威胁。脾脏是重要的外周免疫器官，脾肿大是病变的结果，也是猪链球菌感染的重要临床指标。然而，对脾脏病变相关机制的了解仍然非常有限。在本工作中，我们在小鼠感染模型中进行了研究，以解释这一现象及其相关的免疫调节。获得的结果表明，炎症导致脾肿大，而凋亡导致脾脏淋巴细胞破坏。发现了与猪链球菌诱导的脾脏损伤相关的信号通路，这些通路以前从未与猪链球菌相关。产生的新知识将帮助我们更好地理解猪链球菌发病机制。
