Mechanism by which the combination of Sj CL3 and Sj GAPDH protects against Schistosoma japonicum infection

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IMMUNOLOGY AND HOST-PARASITE INTERACTIONS - ORIGINAL PAPER

Mechanism by which the combination of SjCL3 and SjGAPDH protects against Schistosoma japonicum infection Wenling Huang 1 & Mengjie Gu 1 & Wenjun Cheng 1 & Shuhong Wang 1 & Kaijie Li 1,2 & Qin Ping Zhao 1 & Zhenping Ming 1 & Huifen Dong 1 Received: 24 January 2020 / Accepted: 4 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract A vaccine is an important method to control schistosomiasis. Molecules related to lung-stage schistosomulum are considered potential vaccine candidates. We previously showed that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and cathepsin L3 (CL3) displayed differential expression in the lung-stage schistosomula of Schistosoma japonicum cocultured with host cells. In the present study, we prepared the two proteins and detected the protective effects of SjGAPDH by immunizing mice with this protein alone and in combination with SjCL3 with or without Freund’s adjuvant. Then, we investigated the possible mechanisms underlying S. japonicum infection. The results showed that vaccination of adjuvanted SjGAPDH decreased the worm burden (37.8%) and egg load (38.1%), and the combination of adjuvanted SjGAPDH and SjCL3 further decreased the worm burden (65.6%) and egg load (70.9%) during Schistosoma japonicum infection. However, the immunization of a combination of adjuvant-free SjGAPDH and SjCL3 displayed a lower protective effect (< 15%) than those of the adjuvanted SjCL3, the adjuvanted SjGAPDH, and a combination of adjuvanted SjGAPDH and SjCL3. Flow cytometric results showed that the frequency of regulatory T cells (Tregs) was lower (P < 0.05) in the group with adjuvanted SjGAPDH and SjCL3 (2.61%) than the remaining groups. The enzyme-linked immunosorbent assay (ELISA) results indicated that except for the uninfected and infected control groups, the remaining groups displayed a Th1-type shift in immune responses. These results showed the immunization of SjGAPDH resulted in partial protection (approximately 38%); inoculation with a combination of SjCL3 and SjGAPDH in Freund’s adjuvant resulted in a high immunoprotective effect (> 65%) against Schistosoma japonicum infection in mice, which was possibly caused by the reduced percentage of Tregs and a Th1-type shift in immune responses; and SjCL3 has no adjuvantlike effect, dissimilar to SmCL3. Keywords Schistosoma japonicum . GAPDH . Cathepsin L3 . Immunoprotection . Tregs

Introduction

Section Editor: Ramaswamy Kalyanasundaram Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00436-020-06916-9) contains supplementary material, which is available to authorized users. * Huifen Dong [email protected] 1

Hubei Province Key Laboratory of Allergy and Immunology, Department of Parasitology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China

2

Hubei Provincial Center for Disease Control and Prevention, Wuhan, Hubei Province, China

Schistosomiasis is a severely harmful parasitic zoonosis (