title: The spider acylpolyamine Mygalin is a potent modulator of innate immune responses.
abstract: Mygalin is an antibacterial molecule isolated from the hemocytes of the spider Acanthoscurria gomesiana. It was identified as bis-acylpolyamine spermidine. We evaluated the modulator effects of synthetic Mygalin in the innate immune response. We demonstrate that Mygalin induces IFN-γ synthesis by splenocytes increasing the nitrite secretion by splenocytes and macrophages. A specific inhibitor of iNOS abrogated Mygalin-induced nitrite production in macrophages independent of IFN-γ activation. In addition, Mygalin-activated macrophages produced TNF-α but not IL-1β, demonstrating that Mygalin does not act directly on the inflammasome. Furthermore, this compound did not affect spontaneous or Concanavalin A-induced proliferative responses by murine splenocytes and did not induce IL-5 or apoptosis of splenocytes or bone marrow-derived macrophages. These data provide evidence that Mygalin modulates the innate immune response by inducing IFN-γ and NO synthesis. The combined immune regulatory and antibacterial qualities of Mygalin should be explored as a strategy to enhance immune responses in infection.
authors.affiliation: Laboratorio de Bacteriologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Diego Gabriel
authors.initials: DG
authors.lastname: Mafra
authors.forename: Pedro Ismael
authors.initials: PI
authors.lastname: da Silva
authors.forename: Cynthia Soares
authors.initials: CS
authors.lastname: Galhardo
authors.forename: Rafael
authors.initials: R
authors.lastname: Nassar
authors.forename: Sirlei
authors.initials: S
authors.lastname: Daffre
authors.forename: Maria N
authors.initials: MN
authors.lastname: Sato
authors.forename: Monamaris M
authors.initials: MM
authors.lastname: Borges
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009573:Nitrites / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology*; D013095:Spermidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013112:Spiders / Q000737:chemistry*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: C518064:N1,N8-bis(2,5-dihydroxybenzoyl)spermidine; D009573:Nitrites; D011073:Polyamines; D007371:Interferon-gamma; D013095:Spermidine