Alternative complement pathway is activated in the brains of scrapie-infected rodents

  • Cao Chen
  • Yan Lv
  • Chao Hu
  • Xiao-Feng Xu
  • Ren-Qing Zhang
  • Kang Xiao
  • Yue Ma
  • Li-Ping Gao
  • Jian-Le Li
  • Qiang Shi
  • Jing Wang
  • Qi Shi
  • Xiao-Ping DongEmail author
Original Investigation


Activation of complement system in central nervous system (CNS) of the patients suffering from prion diseases or animal models infected with prion agents experimentally is reported repeatedly, but which pathways are involved in the complement system during prion infection is not well documented. Here, we evaluated the level of complement factor B (CFB), which is the key factor that triggers alterative pathway (AP) of complement in the brain tissues of scrapie-infected mice with various methodologies. We found that the levels of mRNA and protein of CFB significantly increased in the brain tissues of scrapie-infected mice. Morphologically, the increased CFB-specific signal overlapped with the elevated C3 signal in brain sections of scrapie-infected mice, meanwhile overlapped with damaged neurons and activated microglia, but not with the proliferative astrocytes. Additionally, the level of complement factor P (CFP), the key positive regulator of AP, also increased remarkably in the brain tissues of infected mice. The transcriptional levels of CD55 and CD46, two negative regulators of AP, decreased without significance in brain tissues of scrapie-infected mice at the terminal stage. However, the mRNA and protein levels of CFH, another negative regulator of AP, increased. Through the dynamic analyses of the expressions of CFB, CFP, and CFH in brain sections of 139A-infected mice, which were collected at different time-points during incubation period, illustrated time-dependent increase levels of each factor during the incubation period of scrapie infection. Taken together, our data here demonstrate that the AP of complement cascade is activated in the CNS microenvironment during prion infection.


Complement Prion CFB CFP CFH 



This work was supported by National Natural Science Foundation of China (81772197, 81401670, and 81630062), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018RC330004), National Key R&D Program of China (2018YFC1200305 and 2016YFC1202700), SKLID Development Grant (2015SKLID503 and 2016SKLID603), and the Young Scholar Scientific Research Foundation of China CDC (2016A101).

Authors’ contribution

CC and YL designed the study and drafted the manuscript; CH and RQZ carried out the Western blot; XFX, YM, and LPG carried out the IHC; JLL and QS carried out the IFA; QS carried out the real-time PCR; KX and JW performed the statistical analysis. XPD conceived of the study, participated in its design and coordination, and helped to draft the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflict of interest.

Supplementary material

430_2019_641_MOESM1_ESM.jpg (2.5 mb)
Supplementary Fig. 1. Control experiments. (A) Immunofluorescent staining with 2nd-Ab only in brain slices of age-matched healthy control and 139A-infected mice at terminal stage of prion infection (63×). Various 2nd-Ab are indicated on the top. (B) IHC staining with 2nd-Ab only in brain slices of age-matched healthy control, 139A-infected mice and 263 K-infected hamsters at terminal stage of prion infection (40×). Various brain regions are indicated on the top. Brain slices from 3 mice/hamsters in each group (JPEG 2558 kb)
430_2019_641_MOESM2_ESM.jpg (5.5 mb)
Supplementary material 2 (JPEG 5604 kb)
430_2019_641_MOESM3_ESM.jpg (3.4 mb)
Supplementary Fig. 2. Hierarchical scanning of the colocalization between CFB (green) and Iba1 (red) in the cortex of control and 139A-infected mice at end stage of prion infection (63×). (A) age-matched healthy control, (B) 139A-infected mice. The scale is shown at the bottom right of each image. Brain slices from 3 mice/hamsters in each group (JPEG 3502 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.State Key Laboratory for Infectious Disease Prevention and Control, NHC Key Laboratory of Medical Virology and Viral Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University)National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and PreventionBeijingPeople’s Republic of China
  2. 2.Center of Global Public HealthChinese Center for Disease Control and PreventionBeijingPeople’s Republic of China
  3. 3.Center for Biosafety Mega-ScienceChinese Academy of SciencesWuhanPeople’s Republic of China
  4. 4.China Academy of Chinese Medical SciencesBeijingChina

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