title: Somatostatin negatively regulates parasite burden and granulomatous responses in cysticercosis.
abstract: Cysticercosis is an infection of tissues with the larval cysts of the cestode, Taenia solium. While live parasites elicit little or no inflammation, dying parasites initiate a granulomatous reaction presenting as painful muscle nodules or seizures when cysts are located in the brain. We previously showed in the T. crassiceps murine model of cysticercosis that substance P (SP), a neuropeptide, was detected in early granulomas and was responsible for promoting granuloma formation, while somatostatin (SOM), another neuropeptide and immunomodulatory hormone, was detected in late granulomas; SOM's contribution to granuloma formation was not examined. In the current studies, we used somatostatin knockout (SOM(-/-)) mice to examine the hypothesis that SOM downmodulates granulomatous inflammation in cysticercosis, thereby promoting parasite growth. Our results demonstrated that parasite burden was reduced 5.9-fold in SOM(-/-) mice compared to WT mice (P < 0.05). This reduction in parasite burden in SOM(-/-) mice was accompanied by a 95% increase in size of their granulomas (P < 0.05), which contained a 1.5-fold increase in levels of IFN-γ and a 26-fold decrease in levels of IL-1β (P < 0.05 for both) compared to granulomas from WT mice. Thus, SOM regulates both parasite burden and granulomatous inflammation perhaps through modulating granuloma production of IFN-γ and IL-1β.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Mitra
authors.initials: M
authors.lastname: Khumbatta
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Bahrom
authors.initials: B
authors.lastname: Firozgary
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: David John
authors.initials: DJ
authors.lastname: Tweardy
authors.affiliation: Division of Gastroenterology, Department of Medicine, Tufts Medical Center, 800 Washington Street, P.O. Box 233, Boston, MA 02111, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Weinstock
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Gohar
authors.initials: G
authors.lastname: Firozgary
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Zal
authors.initials: Z
authors.lastname: Bhatena
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Tushar
authors.identifier: 0000-0001-6459-4459
authors.initials: T
authors.lastname: Bulsara
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Ricardo
authors.identifier: 0000-0003-1322-5308
authors.initials: R
authors.lastname: Siller
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Prema
authors.identifier: 0000-0002-6798-4839
authors.initials: P
authors.lastname: Robinson
mesh_terms: D000818:Animals; D001921:Brain / Q000469:parasitology / Q000503:physiopathology*; D002589:Cestoda / Q000378:metabolism / Q000472:pathogenicity; D003551:Cysticercosis / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology / Q000503:physiopathology; D006099:Granuloma / Q000235:genetics / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000469:parasitology; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D013004:Somatostatin / Q000235:genetics* / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D041201:Taenia solium / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D053583:Interleukin-1beta; D013373:Substance P; D013004:Somatostatin; D007371:Interferon-gamma