Journal
PARASITOLOGY
Volume 148, Issue 7, Pages 887-894Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0031182021000548
Keywords
Cystic echinococcosis; EgCF; inflammation; macrophages; TRAF6
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Funding
- National Natural Science Foundation of China [82060579, 82060297]
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Echinococcus granulosus cyst fluid (EgCF) attenuates the production of pro-inflammatory factors while increasing IL-10 expression in mouse and human macrophages by promoting TRAF6 proteasomal degradation. This novel mechanism suppresses inflammatory responses by inhibiting NF-kappa B and MAPK signaling pathways.
Echinococcus granulosus sensu lato has complex defence mechanisms that protect it from the anti-parasitic immune response for long periods. Echinococcus granulosus cyst fluid (EgCF) is involved in the immune escape. Nevertheless, whether and how EgCF modulates the inflammatory response in macrophages remains poorly understood. Here, real-time polymerase chain reaction and enzyme-linked immunosorbent assay revealed that EgCF could markedly attenuate the lipopolysaccharide (LPS)-induced production of pro-inflammatory factors including tumour necrosis factor-alpha, interleukin (IL)-12 and IL-6 but increase the expression of IL-10 at mRNA and protein levels in mouse peritoneal macrophages and RAW 264.7 cells. Mechanically, western blotting and immunofluorescence assay showed that EgCF abolished the activation of nuclear factor (NF)-kappa B p65, p38 mitogen-activated protein kinase (MAPK) and ERK1/2 signalling pathways by LPS stimulation in mouse macrophages. EgCF's anti-inflammatory role was at least partly contributed by promoting proteasomal degradation of the critical adaptor TRAF6. Moreover, the EgCF-promoted anti-inflammatory response and TRAF6 proteasomal degradation were conserved in human THP-1 macrophages. These findings collectively reveal a novel mechanism by which EgCF suppresses inflammatory responses by inhibiting TRAF6 and the downstream activation of NF-kappa B and MAPK signalling in both human and mouse macrophages, providing new insights into the molecular mechanisms underlying the E. granulosus-induced immune evasion.
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