TY - JOUR
T1 - Analysis of schistosoma mansoni extracellular vesicles surface glycans reveals potential immune evasion mechanism and new insights on their origins of biogenesis
AU - Dagenais, Maude
AU - Gerlach, Jared Q.
AU - Wendt, George R.
AU - Collins, James J.
AU - Atkinson, Louise E.
AU - Mousley, Angela
AU - Geary, Timothy G.
AU - Long, Thavy
N1 - Funding Information:
Funding: This research was funded by the Natural Sciences and Engineering Research Council of Canada, grant numbers 210349 (T.G.G.), 2020-05880 (T.L.), and the National Institutes of Health Grant R01AI121037 (J.J.C.III).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11
Y1 - 2021/11
N2 - Parasitic helminths are master manipulators of host immunity. Their strategy is complex and involves the release of excreted/secreted products, including extracellular vesicles (EVs). The protein and miRNA contents of EVs have been characterised for many parasitic helminths but, despite reports suggesting the importance of EV surface carbohydrate structures (glycans) in the interactions with target cells and thus subsequent effector functions, little is known about parasite EV glycomics. Using lectin microarrays, we identified several lectins that exhibit strong adhesion to Schistosoma mansoni EVs, suggesting the presence of multiple glycan structures on these vesicles. Interestingly, SNA-I, a lectin that recognises structures with terminal sialic acid, displayed strong affinity for S. mansoni EVs, which was completely abolished by neuraminidase treatment, suggesting sialylation in the EV sample. This finding is of interest, as sialic acids play important roles in the context of infection by aiding immune evasion, affecting target recognition, cell entry, etc., but are not thought to be synthesised by helminths. These data were validated by quantitative analysis of free sialic acid released from EVs following treatment with neuraminidase. Lectin histochemistry and fluorescence in situ hybridisation analyses on whole adult worms suggest the involvement of sub-tegumental cell bodies, as well as the digestive and excretory systems, in the release of EVs. These results support previous reports of EV biogenesis diversity in trematodes and potentially highlight new means of immune modulation and evasion employed by schistosomes.
AB - Parasitic helminths are master manipulators of host immunity. Their strategy is complex and involves the release of excreted/secreted products, including extracellular vesicles (EVs). The protein and miRNA contents of EVs have been characterised for many parasitic helminths but, despite reports suggesting the importance of EV surface carbohydrate structures (glycans) in the interactions with target cells and thus subsequent effector functions, little is known about parasite EV glycomics. Using lectin microarrays, we identified several lectins that exhibit strong adhesion to Schistosoma mansoni EVs, suggesting the presence of multiple glycan structures on these vesicles. Interestingly, SNA-I, a lectin that recognises structures with terminal sialic acid, displayed strong affinity for S. mansoni EVs, which was completely abolished by neuraminidase treatment, suggesting sialylation in the EV sample. This finding is of interest, as sialic acids play important roles in the context of infection by aiding immune evasion, affecting target recognition, cell entry, etc., but are not thought to be synthesised by helminths. These data were validated by quantitative analysis of free sialic acid released from EVs following treatment with neuraminidase. Lectin histochemistry and fluorescence in situ hybridisation analyses on whole adult worms suggest the involvement of sub-tegumental cell bodies, as well as the digestive and excretory systems, in the release of EVs. These results support previous reports of EV biogenesis diversity in trematodes and potentially highlight new means of immune modulation and evasion employed by schistosomes.
KW - Exosomes
KW - Extracellular vesicles
KW - Glycans
KW - Helminths
KW - Lectin histochemistry
KW - Lectin microarray
KW - Schistosomes
KW - Secretome
KW - Sialic acid
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U2 - 10.3390/pathogens10111401
DO - 10.3390/pathogens10111401
M3 - Article
C2 - 34832557
AN - SCOPUS:85118731962
SN - 2076-0817
VL - 10
JO - Pathogens
JF - Pathogens
IS - 11
M1 - 1401
ER -