Neuroprotection during Neospora caninum Infection is Related to the Release of Neurotrophic Factors BDNF and NGF

Activation of the Kynurenine Pathway and Production of Inflammatory Cytokines by Astrocytes and Microglia Infected WithNeospora caninum

“…CCL5 also plays a role as neuromodulator, presenting protective properties in CNS cells. 28 The combination of CCL5, CCL2, IL-10 mediators, and arginase activity in the results herein presented corroborates with the mechanisms of evasion and encystment of neurotropic parasites described by Hemphill et al 26 and with an induced tissue preservation observed in a similar model by Grangeiro et al 14 …”

“…Primary cultures of glial cells were obtained from the cerebral cortex of newborn Wistar rats (0-48 hours) and performed as described previously. 14 Briefly, cerebral hemispheres and meninges were removed and the tissue was mechanically dissociated into individual cells in Dulbecco’s modified Eagle’s medium (DMEM) with HAM F12 (1:1) (Gibco, Grand Island, NY) with the aid of a Pasteur pipette. The cells were suspended in DMEM HAM F12 medium, supplemented with 10% of FBS, sodium bicarbonate (35 mM) (Sigma Aldrich, St. Louis, U.S.A), 100 UI/mL penicillin/streptomycin, seeded at a density of 2.2 × 10 4 cells/cm 2 in 24-well pre-coated plates (TPP, Trasadingen, Switzerland) with 10 µg/mL poly-L-lysine (Sigma Chemical, Darmstadt, Germany) and cultured in humidified atmosphere with 5% CO 2 at 37°C.…”

“…After confluence, glial cells were infected with Neospora caninum in the proportion of 1 parasite per cell (1:1) for 24 hours, according to the protocol. 14 After this period, the conditioned culture medium (cellular secretome) was collected and filtered through a 0.2-µm membrane pore and stored for further molecular analysis and treatment of glia-neuron co-cultures. The glial cells were characterized by immunocytochemistry structural markers of microglia and astrocytes.…”

“…Neospora caninum , an apicomplexa parasite that causes neosporosis, has tropism for the nervous tissue, where it is encysted. 10 Some experimental models of N. caninum infection have shown that this tissue reacts to the invader through biochemical and immunological mechanisms, 11 particularly the release of IL-10 and TNF 12 , 13 besides the induction of neurotrophic factors 14 that allow the parasite to survive and promote a consequent neuro-preservation. 11 - 14 On the other hand, the infection of glial-neuron co-cultures with N. caninum tachyzoites after modulated by IFN-γ showed preservation of neurite outgrowth and induced the activation of indolamine 2, 3 dioxygenase (IDO), the first and rate-limiting enzyme of tryptophan catabolism through the KP, controlling the parasite proliferation.…”

From Signaling Pathways to Distinct Immune Responses: Key Factors for Establishing or Combating Neospora caninum Infection in Different Susceptible Hosts

“…SERPINA14 has a regulatory decrease of the immunosuppressive effect of progesterone in cases of pregnancy [201,202]. Although there is an unknown immunological role, host factors such as neurotropic proteins in rat tissues [203], cholesterol and lipoproteins in human and bovine cell lines [204], purine, acetylcholinesterase and butyrylcholinesterase in gerbil tissues and blood [205,206] seem to play a role in N. caninum infection in mentioned hosts because of marked altered levels among infected and non-infected hosts. Furthermore, a previous report indicated that cathelicidins (host defence peptides in human cells) showed higher expression levels in macrophages infected with live tachyzoites of N. caninum than naïve cells.…”