Echinococcus granulosus antigen B acts as an LPS-scavenging lipoprotein in vitro preventing TLR4-mediated activation of dendritic cells
Echinococcus granulosus sensu lato antigen B (EgAgB) is a major parasite lipoprotein, produced by the hydatid and released at the host-parasite interface. Accumulating evidence supports that EgAgB may exert immunomodulatory effects on myeloid cells; however, the underlying molecular mechanisms remai...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | , , , , , , , , , |
| Format: | article |
| Language: | English |
| Published: |
2026
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/20.500.12381/5492 https://doi.org/10.1128/iai.00361-25 |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1868890045249748992 |
|---|---|
| author | Lagos Magallanes, Sofía |
| author2 | Beasley Lomazzi, Anaclara Zamarreño, Fernando Carrión, Federico Fló, Martín Dutto, Jerónimo Julve, Josep Costabel, Marcelo Maccioni, Mariana Folle, Ana Maite Ferreira, Ana María |
| author2_role | author author author author author author author author author author |
| author_browse | Beasley Lomazzi, Anaclara Carrión, Federico Costabel, Marcelo Dutto, Jerónimo Ferreira, Ana María Fló, Martín Folle, Ana Maite Julve, Josep Lagos Magallanes, Sofía Maccioni, Mariana Zamarreño, Fernando |
| author_facet | Lagos Magallanes, Sofía Beasley Lomazzi, Anaclara Zamarreño, Fernando Carrión, Federico Fló, Martín Dutto, Jerónimo Julve, Josep Costabel, Marcelo Maccioni, Mariana Folle, Ana Maite Ferreira, Ana María |
| author_role | author |
| collection | REDI |
| dc.creator.none.fl_str_mv | Lagos Magallanes, Sofía Beasley Lomazzi, Anaclara Zamarreño, Fernando Carrión, Federico Fló, Martín Dutto, Jerónimo Julve, Josep Costabel, Marcelo Maccioni, Mariana Folle, Ana Maite Ferreira, Ana María |
| dc.date.none.fl_str_mv | 2026-04-10T14:45:35Z 2026-04-10T14:45:35Z 2026-01-13 |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/20.500.12381/5492 FCE_1_2021_1_166731 https://doi.org/10.1128/iai.00361-25 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | ASM Journals |
| dc.relation.none.fl_str_mv | https://pubmed.ncbi.nlm.nih.gov/41400481/ |
| dc.rights.none.fl_str_mv | Acceso abierto info:eu-repo/semantics/openAccess Reconocimiento 4.0 Internacional. (CC BY) |
| dc.source.none.fl_str_mv | Infection and Immunity reponame:REDI instname:Agencia Nacional de Investigación e Innovación instacron:Agencia Nacional de Investigación e Innovación |
| dc.subject.none.fl_str_mv | Echinococcus granulosus Parasite lipoprotein Antigen B Dendritic cell activation Inmunomodulation LPS Ciencias Naturales y Exactas Ciencias Biológicas |
| dc.title.none.fl_str_mv | Echinococcus granulosus antigen B acts as an LPS-scavenging lipoprotein in vitro preventing TLR4-mediated activation of dendritic cells |
| dc.type.none.fl_str_mv | Artículo info:eu-repo/semantics/article Aceptado info:eu-repo/semantics/acceptedVersion |
| description | Echinococcus granulosus sensu lato antigen B (EgAgB) is a major parasite lipoprotein, produced by the hydatid and released at the host-parasite interface. Accumulating evidence supports that EgAgB may exert immunomodulatory effects on myeloid cells; however, the underlying molecular mechanisms remain poorly understood. We examined the impact of native EgAgB (nEgAgB) and recombinant EgAgB8/1 (rEgAgB) on lipopolysaccharide (LPS)-induced activation of bone marrow-derived dendritic cells (BMDC), to help elucidate these mechanisms. Both immunoaffinity-purified nEgAgB or rEgAgB induced modest BMDC activation, indicated by the production of IL-6, IL-12p40, and nitric oxide, but not IFN-β. This activation was primarily attributed to LPS traces in EgAgB preparations since it was nearly abolished by a specific TLR4 inhibitor and in Tlr4-/- BMDC, while EgAgB binding to BMDC was TLR4-independent. Notably, both nEgAgB and rEgAgB inhibited LPS-induced cytokine and nitric oxide production, and disrupted TLR4 dimerization and endocytosis. Competitive binding assays showed that EgAgB and human high-density lipoprotein (hHDL) similarly inhibited LPS binding to macrophages and BMDC; however, EgAgB more effectively suppressed LPS-induced cytokine secretion. Contrastingly, EgAgB did not modulate BMDC responses to lipoteichoic acid, unlike hHDL. Using dynamic light scattering and an ELISA-like assay, we demonstrated a higher potential of EgAgB to bind LPS than hHDL. Additionally, docking analyses suggest the presence of a defined LPS-binding interface in EgAgB8/1 subunit. Overall, these findings reveal a novel binding property of EgAgB, which enables it to act as an extracellular LPS scavenger, interfering with TLR4-mediated LPS recognition and downstream proinflammatory responses in myeloid cells. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | anni_4e99d36fc2785d975e45336d2d3ad068 |
| identifier_str_mv | FCE_1_2021_1_166731 |
| instacron_str | Agencia Nacional de Investigación e Innovación |
| institution | Agencia Nacional de Investigación e Innovación |
| instname_str | Agencia Nacional de Investigación e Innovación |
| language | eng |
| network_acronym_str | anni |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:redi.anii.org.uy:20.500.12381/5492 |
| publishDate | 2026 |
| publishDateSort | 2026 |
| publisher.none.fl_str_mv | ASM Journals |
| reponame_str | REDI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | Acceso abierto Reconocimiento 4.0 Internacional. (CC BY) |
| spelling | Echinococcus granulosus antigen B acts as an LPS-scavenging lipoprotein in vitro preventing TLR4-mediated activation of dendritic cellsLagos Magallanes, SofíaBeasley Lomazzi, AnaclaraZamarreño, FernandoCarrión, FedericoFló, MartínDutto, JerónimoJulve, JosepCostabel, MarceloMaccioni, MarianaFolle, Ana MaiteFerreira, Ana MaríaEchinococcus granulosusParasite lipoproteinAntigen BDendritic cell activationInmunomodulationLPSCiencias Naturales y ExactasCiencias BiológicasEchinococcus granulosus sensu lato antigen B (EgAgB) is a major parasite lipoprotein, produced by the hydatid and released at the host-parasite interface. Accumulating evidence supports that EgAgB may exert immunomodulatory effects on myeloid cells; however, the underlying molecular mechanisms remain poorly understood. We examined the impact of native EgAgB (nEgAgB) and recombinant EgAgB8/1 (rEgAgB) on lipopolysaccharide (LPS)-induced activation of bone marrow-derived dendritic cells (BMDC), to help elucidate these mechanisms. Both immunoaffinity-purified nEgAgB or rEgAgB induced modest BMDC activation, indicated by the production of IL-6, IL-12p40, and nitric oxide, but not IFN-β. This activation was primarily attributed to LPS traces in EgAgB preparations since it was nearly abolished by a specific TLR4 inhibitor and in Tlr4-/- BMDC, while EgAgB binding to BMDC was TLR4-independent. Notably, both nEgAgB and rEgAgB inhibited LPS-induced cytokine and nitric oxide production, and disrupted TLR4 dimerization and endocytosis. Competitive binding assays showed that EgAgB and human high-density lipoprotein (hHDL) similarly inhibited LPS binding to macrophages and BMDC; however, EgAgB more effectively suppressed LPS-induced cytokine secretion. Contrastingly, EgAgB did not modulate BMDC responses to lipoteichoic acid, unlike hHDL. Using dynamic light scattering and an ELISA-like assay, we demonstrated a higher potential of EgAgB to bind LPS than hHDL. Additionally, docking analyses suggest the presence of a defined LPS-binding interface in EgAgB8/1 subunit. Overall, these findings reveal a novel binding property of EgAgB, which enables it to act as an extracellular LPS scavenger, interfering with TLR4-mediated LPS recognition and downstream proinflammatory responses in myeloid cells.Universidad de la República. Comisión Sectorial de Investigación CientíficaPrograma de Desarrollo de las Ciencias BásicasAgencia Nacional de Investigación e InnovaciónAgencia Estatal de Investigación (España)Ministerio de Ciencia e Innovación (España)ASM Journals2026-04-10T14:45:35Z2026-04-10T14:45:35Z2026-01-13Artículoinfo:eu-repo/semantics/articleAceptadoinfo:eu-repo/semantics/acceptedVersionhttps://hdl.handle.net/20.500.12381/5492FCE_1_2021_1_166731https://doi.org/10.1128/iai.00361-25Infection and Immunityreponame:REDIinstname:Agencia Nacional de Investigación e Innovacióninstacron:Agencia Nacional de Investigación e Innovaciónenghttps://pubmed.ncbi.nlm.nih.gov/41400481/Acceso abiertoinfo:eu-repo/semantics/openAccessReconocimiento 4.0 Internacional. (CC BY)oai:redi.anii.org.uy:20.500.12381/54922026-06-16T05:02:12Z |
| spellingShingle | Echinococcus granulosus antigen B acts as an LPS-scavenging lipoprotein in vitro preventing TLR4-mediated activation of dendritic cells Lagos Magallanes, Sofía Echinococcus granulosus Parasite lipoprotein Antigen B Dendritic cell activation Inmunomodulation LPS Ciencias Naturales y Exactas Ciencias Biológicas |
| status_str | acceptedVersion |
| title | Echinococcus granulosus antigen B acts as an LPS-scavenging lipoprotein in vitro preventing TLR4-mediated activation of dendritic cells |
| title_full | Echinococcus granulosus antigen B acts as an LPS-scavenging lipoprotein in vitro preventing TLR4-mediated activation of dendritic cells |
| title_fullStr | Echinococcus granulosus antigen B acts as an LPS-scavenging lipoprotein in vitro preventing TLR4-mediated activation of dendritic cells |
| title_full_unstemmed | Echinococcus granulosus antigen B acts as an LPS-scavenging lipoprotein in vitro preventing TLR4-mediated activation of dendritic cells |
| title_short | Echinococcus granulosus antigen B acts as an LPS-scavenging lipoprotein in vitro preventing TLR4-mediated activation of dendritic cells |
| title_sort | Echinococcus granulosus antigen B acts as an LPS-scavenging lipoprotein in vitro preventing TLR4-mediated activation of dendritic cells |
| topic | Echinococcus granulosus Parasite lipoprotein Antigen B Dendritic cell activation Inmunomodulation LPS Ciencias Naturales y Exactas Ciencias Biológicas |
| url | https://hdl.handle.net/20.500.12381/5492 https://doi.org/10.1128/iai.00361-25 |