Fig 1.
Schematic diagram of T. solium infection showing the different steps of human and porcine cysticercosis including human NCC. NCC, neurocysticercosis.
Fig 2.
Cyst involution in brain parenchyma and associated immunopathogenesis.
The presence of viable vesicular cysts (A) is usually asymptomatic and associated with suppression of the host immune responses through induction of anti-inflammatory cytokines. Upon successful attack of the host immune system, the cyst passes through a series of involuting stages (B–D). The BBB is disrupted, and granuloma, mainly composed of macrophages, granulocytes, and lymphocytes, encompasses the cyst that contracts (colloidal stage) (B) and becomes nodular and the scolex granulated (granular-nodular stage) (C); this is followed by the formation of collagenous and fibrotic structures and calcification of the cyst (calcified stage) (D). Each involuting stage of the cyst releases material (ES and Ag) and elicits an inflammatory reaction and release of mediators in the brain that lead to the development of pathology and symptoms (pale orange box). Ag, cyst antigen; B, lymphocyte B; BBB, blood–brain barrier; EO, eosinophil; ES, excretory–secretory; EV, extracellular vesicle; IFN, interferon; IL, interleukin; M, macrophage; Mi, microglia/dendritic cell; NE, neutrophil; TGF-ß, transforming growth factor beta; Th, T helper cell; TNF, tumor necrosis factor.
Table 1.
Key cellular and humoral effectors associated with parenchymal and extraparenchymal NCC.
Fig 3.
Host immune regulation during parenchymal NCC.
Viable cyst releases ES products and EVs that interact with resident brain cells (microglia and DCs) and induce AAMs, which suppress adhesion molecules and local Th1 response via TGF-ß and IL-10. Excreted products reach peripheral system where they drive the expansion of suppressive Tregs from CD4+ cells through the alteration of the maturation of DCs. Furthermore, cyst products inhibit complement C1q activity and prevent the infiltration and migration of neutrophils, eosinophils and MO from the peripheral system into the brain via production of immunomodulatory cytokines and blocking of chemokines and adhesion molecules. AAM, alternatively activated macrophages; B, ; BBB, blood–brain barrier; CCL, chemokine C-C ligand; CD4, cluster of differentiation 4; C1q, complement first component; CTLA-4, cytotoxic T-lymphocyte associated protein 4; CXCL, chemokine C-X-C ligand; DC, dendritic cell; EO, eosinophil; ES, excretory–secretory; EV, extracellular vesicle; ICAM-1, intercellular adhesion molecule 1; iDC, immature DC; IL, interleukin; Mi, microglia; MO, monocytes; NCC, neurocysticercosis; TGF-ß, transforming growth factor beta; Th, T helper; Treg, regulatory T cell; VCAM-1, vascular cell adhesion protein 1.