Immunomodulatory action of excretory-secretory products of Angiostrongylus cantonensis in a mouse tumour model
- PDF / 2,556,196 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 79 Downloads / 151 Views
IMMUNOLOGY AND HOST-PARASITE INTERACTIONS - ORIGINAL PAPER
Immunomodulatory action of excretory-secretory products of Angiostrongylus cantonensis in a mouse tumour model Yajun Lu 1
&
Yuxiao Yang 1 & Siqi Yang 1 & Qianfeng Xia 1
Received: 20 March 2020 / Accepted: 30 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Excretory-secretory products (ESPs) of parasitic helminths are well known to exert immunostimulation and immunomodulation in hosts. Immune regulation plays a key role in anti-tumour therapy. The present study explored the anti-tumour effect of ESPs released by Angiostrongylus cantonensis. In Hepa1-6 mouse tumour models, ESPs significantly reduced tumour growth. Tumour-bearing mice treated with ESPs had significantly higher CD3+, CD4+, and CD8+ T cell counts than those treated with Freund’s adjuvant. In vitro, human hepatocarcinoma HepG2 cells, human lung cancer A549 cells, and normal human liver HL7702 cells were co-incubated with ESPs for 24 h and 48 h. ESPs significantly accelerated HepG2 apoptosis but had no inhibitory effect on the proliferation of A549 and HL-7702 cells. Apoptotic HepG2 cells displayed condensed nuclei, apoptotic bodies, and swollen endoplasmic reticulum (ER). Expression of the endoplasmic reticulum stress (ERS)-related factors activating transcription factor 6 (ATF6) and C/EBP-homologous protein (CHOP) in HepG2 cells increased with increasing ESP concentration and treatment time. Calreticulin (CRT) is a key effector protein of ESPs, and recombinant calreticulin (rCRT) was produced in BL21 Escherichia coli (E. coli). In contrast to ESPs, rCRT markedly reduced the proliferation of HepG2 cells. The expression levels of ATF6 and CHOP in HepG2 cells treated with 30 μg/mL rCRT significantly increased at 48 h. Notably, these findings synergistically suggest that ESPs and rCRT are promising candidates for anti-tumour immunotherapy. Keywords Excretory-secretory products . Calreticulin . Angiostrongylus cantonensis . Tumour . Apoptosis . Endoplasmic reticulum stress
Introduction Accumulating evidence shows that ESPs derived from parasitic helminths play a definite immunomodulatory role in the host response to parasite infection. Endoparasites continuously release ESPs into the microenvironment of the host-parasite interface (Ilic et al. 2012; Radovic et al. 2015), irrespective of whether they migrate or settle at a tissue site (SofronicMilosavljevic et al. 2013). Exogenous peptide ESPs can provoke the host immune response, profoundly affect host Handling Editor: Julia Walochnik * Qianfeng Xia [email protected] 1
Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou 571199, Hainan, China
immunomodulatory function, and thus produce an antitumour effect (Luo et al. 2017). Additionally, ESPs of Angiostrongylus cantonensis (Chen, 1935) (Nematoda: Metastrongylidae) (Yang et al. 2013) third-stage larvae are directly exposed to the host immun
Data Loading...
