TY - JOUR
T1 - Absence of the SP/SP receptor circuitry in the substance P-precursor knockout mice or SP receptor, neurokinin (NK)1 knockout mice leads to an inhibited cytokine response in granulomas associated with murine Taenia crassiceps infection
AU - Garza, Armandina
AU - Weinstock, Joel
AU - Robinson, Prema
PY - 2008/12
Y1 - 2008/12
N2 - Neurocysticercosis, caused by the cestode Taenia solium, is the most common parasitic infection of the human central nervous system that leads to seizures. Taenia crassiceps cysticercosis in mice is an experimental model for Taenia solium cysticercosis. Similar to the human infection, live parasites cause little or no granulomatous inflammation. Dying parasites initiate a granulomatous reaction. The neuropeptide substance P (SP) stimulates T-helper (Th) 1 cytokine production. In the current study, we determined whether absence of SP/SP receptor circuitry in the SP-precursor, preprotachykinin, knockout or SP-receptor, neurokinin (NK)1, knockout mice affected granuloma cytokine production. We hence compared the levels of Th1 cytokines interleukin (IL)-2 and interferon (IFN)-γ and levels of Th2/immunoregulatory cytokines IL-4 and IL-10 by enzyme-linked immunosorbent assay in T. crassiceps-induced granulomas derived from infected C57BL/6 wild-type (WT) versus SP-precursor knockout and NK1 knockout mice. We found that mean levels of IL-2, IFN-γ, IL-4, and IL-10 in infected WT-derived granulomas were significantly higher than those of granulomas derived from infected SP-precursor knockout or the NK1 receptor (NK1R) knockout mice. Levels of Th2/immunoregulatory cytokines IL-4 and IL-10 were higher in early stage granulomas (histologically staged on basis of evidence of parasite remnants) versus late stage granulomas (no parasite remnants) of both knockouts, whereas the reverse was noted in WT-derived granulomas. This study established that the absence of an SP/SP receptor circuitry in the SP-precursor knockout mice or NK1 receptor knockout mice led to an inhibited cytokine response.
AB - Neurocysticercosis, caused by the cestode Taenia solium, is the most common parasitic infection of the human central nervous system that leads to seizures. Taenia crassiceps cysticercosis in mice is an experimental model for Taenia solium cysticercosis. Similar to the human infection, live parasites cause little or no granulomatous inflammation. Dying parasites initiate a granulomatous reaction. The neuropeptide substance P (SP) stimulates T-helper (Th) 1 cytokine production. In the current study, we determined whether absence of SP/SP receptor circuitry in the SP-precursor, preprotachykinin, knockout or SP-receptor, neurokinin (NK)1, knockout mice affected granuloma cytokine production. We hence compared the levels of Th1 cytokines interleukin (IL)-2 and interferon (IFN)-γ and levels of Th2/immunoregulatory cytokines IL-4 and IL-10 by enzyme-linked immunosorbent assay in T. crassiceps-induced granulomas derived from infected C57BL/6 wild-type (WT) versus SP-precursor knockout and NK1 knockout mice. We found that mean levels of IL-2, IFN-γ, IL-4, and IL-10 in infected WT-derived granulomas were significantly higher than those of granulomas derived from infected SP-precursor knockout or the NK1 receptor (NK1R) knockout mice. Levels of Th2/immunoregulatory cytokines IL-4 and IL-10 were higher in early stage granulomas (histologically staged on basis of evidence of parasite remnants) versus late stage granulomas (no parasite remnants) of both knockouts, whereas the reverse was noted in WT-derived granulomas. This study established that the absence of an SP/SP receptor circuitry in the SP-precursor knockout mice or NK1 receptor knockout mice led to an inhibited cytokine response.
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U2 - 10.1645/GE-1481.1
DO - 10.1645/GE-1481.1
M3 - Article
C2 - 18576810
AN - SCOPUS:58549101305
SN - 0022-3395
VL - 94
SP - 1253
EP - 1258
JO - Journal of Parasitology
JF - Journal of Parasitology
IS - 6
ER -