Trypanosoma evansi evades host innate immunity by releasing extracellular vesicles to activate TLR2-AKT signaling pathway

Abstract

Surra, one of the most important animal diseases with economic consequences in Asia and South America, is caused by Trypanosoma evansi . However, the mechanism of immune evasion by T. evansi has not been extensively studied. In the present study, T. evansi extracellular vesicles (TeEVs) were characterized and the role of TeEVs in T. evansi infection were examined. The results showed that T. evansi and TeEVs could activate TLR2-AKT pathway to inhibit the secretions of IL-12p40, IL-6, and TNF-α in mouse BMDMs. TLR2 −/- mice and mice with a blocked AKT pathway were more resistant to T. evansi infection than wild type (WT) mice, with a significantly lower infection rate, longer survival time and less parasite load, as well as an increased secretion level of IL-12p40 and IFN-γ. Kinetoplastid membrane protein-11 (KMP-11) of TeEVs could activate AKT pathway and inhibit the productions of IL-12p40, TNF-α, and IL-6 in vitro . TeEVs and KMP-11 could inhibit the productions of IL-12p40 and IFN-γ, promote T. evansi proliferation and shorten the survival time of infected mice in vivo . In conclusion, T. evansi could escape host immune response through inhibiting the productions of inflammatory cytokines via secreting TeEVs to activate TLR2-AKT pathway. KMP-11 in TeEVs was involved in promoting T. evansi infection. Extracellular vesicles (EVs) secreted by Trypanosoma evansi ( T. evansi ) activate the TLR2-AKT signaling pathway to inhibit the production of inflammatory cytokines, thereby escaping the host’s immune response. Kinetoplastid membrane protein-11 (KMP-11) in EVs is related to the promotion of T. evansi infection via AKT pathway.

Impact of pulmonary African trypanosomes on the immunology and function of the lung

“…Intercellular communication between parasites can even transfer serum resistance factors from human pathogenic to non-pathogenic strains 22 . The release of EVs also modulates the host immune response in favour of trypanosome replication 49 – 51 . The biological importance of the extensive EV release and metabolic adaptations to the high oxygen tension in the lung remains to be understood.…”

Toll-like receptor 2 signaling pathway activation contributes to a highly efficient inflammatory response in Japanese encephalitis virus-infected mouse microglial cells by proteomics

“…Microglia have a diverse set of pattern recognition receptors, including members of the Toll-like receptor and phagocytic receptor families; these work together to detect and remove microorganisms that have infiltrated the CNS parenchyma ( Mariani and Kielian, 2009 ). TLR2 is an innate immune sensor on the cell surface that may identify ligands from viruses, fungi, bacteria, and parasites ( Wei et al, 2021 ). TLR2 has been found to sense various viral proteins after infection, including Epstein-Barr virus dUTPase, cytomegalovirus glycoprotein B, and hepatitis B virus capsid ( Wei et al, 2021 ).…”

“…TLR2 is an innate immune sensor on the cell surface that may identify ligands from viruses, fungi, bacteria, and parasites ( Wei et al, 2021 ). TLR2 has been found to sense various viral proteins after infection, including Epstein-Barr virus dUTPase, cytomegalovirus glycoprotein B, and hepatitis B virus capsid ( Wei et al, 2021 ). JEV induces neuroinflammation, which has been identified as a significant element in JEV pathogenesis in humans, including immune cell infiltration and neuronal degeneration ( Misra and Kalita, 2010 ).…”

“…However, whether JEV infection causes an inflammatory response only through the TLR3 pathways is a matter of concern. Previous research has shown that TLR2 mediates a parasite-induced inflammatory response ( Wei et al, 2021 ), although the mechanism underlying the TLR2-mediated inflammatory response in JEV infection has yet to be elucidated. The activation of TLR2 and its downstream pathways following JEV infection have still to be investigated.…”

DDIT3 antagonizes innate immune response to promote bovine alphaherpesvirus 1 replication via the DDIT3-SQSTM1-STING pathway

“…The separated proteins were transferred to PVDF membranes and subsequently blocked with 8% nonfat dry milk in TBST (PS103, EpiZyme Biotechnology). The blocked membranes were incubated with the relevant primary antibodies, washed 5 times with TBST, and incubated with appropriate secondary antibodies as previously described [ 50 ]. Protein bands were detected using an ECL Chemiluminescence Kit (SQ201, EpiZyme Biotechnology).…”