Brain Granulomas in Neurocysticercosis Patients Are Associated with a Th1 and Th2 Profile

Abstract

Neurocysticercosis (NCC) is a common central nervous system (CNS) infection caused by Taenia solium metacestodes. Despite the well-documented importance of the granulomatous response in the pathogenesis of this infection, there is limited information about the types of cells and cytokines involved. In fact, there has been limited characterization of human brain granulomas with any infectious agent. In the present study a detailed histological and immunohistochemical analysis of the immune response was performed on eight craniotomy specimens where a granuloma surrounded each T. solium metacestode. The results indicated that in all the specimens there was a dying parasite surrounded by a mature granuloma with associated fibrosis, angiogenesis, and an inflammatory infiltrate. The most abundant cell types were plasma cells, B and T lymphocytes, macrophages, and mast cells. Th1 cytokines were prevalent and included gamma interferon, interleukin-18 (IL-18), and the immunosuppressive, fibrosis-promoting cytokine transforming growth factor ␤. The Th2 cytokines IL-4, IL-13, and IL-10 were also present. These observations indicate that a chronic immune response is elicited in the CNS environment with multiple cell types that together secrete inflammatory and anti-inflammatory cytokines. In addition, both collagen type I and type III deposits were evident and could contribute to irreversible nervous tissue damage in NCC patients.

IFN‐γ‐induced IDO and WRS expression in microglia is differentially regulated by IL‐4

“…In pathologies where IL-4 or IL-13 would be present, IFN-γ induced IDO would be upregulated but WRS would be downregulated. Expression of IFN-γ and IL-4 are found simultaneously in the brain in human neurocysticercosis and mouse cryptocococcal meningoencephalitis (Maffei et al 2004;Restrepo et al 2001). IDO expressing cells are indeed present in granulomatous inflammation (Popov et al 2006).…”

Predictors of Lesion Calcification in Patients with Solitary Cysticercus Granuloma and New-Onset Seizures

“…Matrix metalloproteinases (MMP-2 and MMP-9) have been shown to be responsible for maintaining blood-brain barrier permeability. 19,20 The perilesional edema seen around a calcified lesion, possibly, has a different pathogenesis than perilesional edema present around a solitary cysticercus granuloma. Histopathologically, a degenerated cysticercus is characterized with intense intracystic and capsular inflammatory response (consisting of mononuclear cells, some plasma cells, and a few eosinophils).…”

“…We could have used magnetic resonance imaging, which is superior in quantifying perilesional edema and in demonstration of scolex within the lesion. 20 Association of calcified neurocysticercosis with hippocampal atrophy could have been studied in patients with refractory epilepsy, but which required the use of magnetic resonance imaging.…”

Contribution of myeloid cell subsets to liver fibrosis in parasite infection

“…Subsequently, IL-4Rα + M2, induced by IL-4 and IL-13, are required to suppress the IL-12/Th1/M1 and IL-23/Th17 response, thereby allowing the emergence of regulatory T cells that promote the production of IL-10 and TGFβ. These cytokines limit the IL-17-mediated recruitment of neutrophils and promote the repair/wound healing of the intestinal wall as worms cross from mesenteric blood to the lumen for expulsion, avoiding destruction of liver and gut barrier integrity as well as exposure of the host to lethal septicaemia in acute infection [7][8][9] weeks post-infection (wkpi)]. IFNγ also regulates the Th17 response and thereby favours the transition from an acute to a chronic infection [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46].…”

“…Here, we provide an overview of the mechanisms by which clinically important parasites -such as Schistosoma mansoni and S. japonicum, and hydatid cysts from Echinococcus multilocularis that localize primarily in the liverdrive liver fibrogenesis following their interaction with myeloid cell subsets. Other parasites, such as Trypanosoma cruzi , Taenia solium, Nippostrongylus brasiliensis and Schistosoma haematobium, inducing fibrosis in the heart, brain, lungs and bladder, respectively [9][10][11][12][13][14][15], and liver flukes, such as Clonorchis sinensis and Opisthorchis viverrini , causing bile periductal fibrosis, which increases the risk for cholangiocarcinoma [16][17][18][19][20], are not covered here, due to the marginal information on the phenotype, function and activation status of myeloid cells in these pathogenic processes.…”