Substance P signaling contributes to granuloma formation in Taenia crassiceps infection, a murine model of cysticercosis.
Cysticercosis is an infection with larval cysts of the cestode Taenia solium. Through pathways that are incompletely understood, dying parasites initiate a granulomatous reaction that, in the brain, causes seizures. Substance P (SP), a neuropeptide involved in pain-transmission, contributes to inflammation and previously was detected in granulomas associated with dead T. crassiceps cysts. To determine if SP contributes to granuloma formation, we measured granuloma-size and levels of IL-1beta, TNF-alpha, and IL-6 within granulomas in T. crassiceps-infected wild type (WT) mice and mice deficient in SP-precursor (SPP) or the SP-receptor (neurokinin 1, NK1). Granuloma volumes of infected SPP- and NK1-knockout mice were reduced by 31 and 36%, respectively, compared to WT mice (P < .05 for both) and produced up to 5-fold less IL-1beta, TNF-alpha, and IL-6 protein. Thus, SP signaling contributes to granuloma development and proinflammatory cytokine production in T. crassiceps infection and suggests a potential role for this mediator in human cystercercosis.
Section of Infectious Disease, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Armandina
A
Garza
David J
DJ
Tweardy
Joel
J
Weinstock
Balaji
B
Viswanathan
Prema
P
Robinson
D000818:Animals; D003551:Cysticercosis / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006099:Granuloma / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013373:Substance P / Q000378:metabolism*; D013621:Taenia; D013622:Taeniasis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D015850:Interleukin-6; D018040:Receptors, Neurokinin-1; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P