Table 2.
Cellular immune response against N. caninum involving various immune cells.
| Host Factors | Host Species | Parasite or Its Molecule | Impacts and Outcomes | References |
|---|---|---|---|---|
| Macrophages | C57BL/6J mice | N. caninum tachyzoites (Nc-1) | Marked increase in recruitment of macrophages to site of infection associated with increased IL-6 and IL-12p40 during N. caninum infection. Macrophage-depleted mice exhibited high susceptibility to N. caninum infection. |
[141] |
| Macrophages | BALB/c mice | NcGRA6 (Nc-1) | Peritoneal macrophages treated with different doses of recombinant NcGRA6 induced cytokine production IL-12. | [142] |
| Macrophages | Cattle | N. caninum tachyzoites (Nc-Spain7 and Nc-Spain1H) | Infection of cattle accompanied with higher genes expression involved in pathogen recognition, chemotaxis and proinflammatory and regulatory cytokine secretion. | [143] |
| Macrophages | Cattle | N. caninum tachyzoites (Nc-Spain7 and Nc-Spain1H) | Macrophages infected with Nc-Spain1H showed high ROS production and IL12p40 expression, compared to cells infected with Nc-Spain7. IL-10 was increased in macrophages infected with both isolates. Infected macrophages exhibited lower expression of MHC Class II, CD86, and CD1b molecules than uninfected cells. |
[144] |
| Monocytes | Cattle | N. caninum tachyzoites (Nc-Liv) | Neonatal animals had a marked higher percentage of CD14+ monocytes, and adult monocytes showed higher parasitism than neonatal monocytes. Greater secretion of IL-1β was observed in neonates than adult monocytes. |
[136] |
| Dendritic cells | C57BL/6 mice | N. caninum tachyzoites (Nc-1) | Cytokine expression analysis revealed that both viable and nonviable parasites stimulated BMDCs to express IL-12p40, IL-10, and TNF-α. | [145] |
| Dendritic cells | BALB/c mice | N. caninum tachyzoites (Nc-1) | The response to whole tachyzoites (live, heat-killed, freeze-killed) or whole-cell tachyzoite lysate (soluble, insoluble antigen) stimulated moderate-to-high levels of IL-12, IFN-γ, and TNF-α. | [146] |
| Dendritic cells and macrophages | Murine H 2k cell line and CBA/J mice | N. caninum tachyzoites (Nc-1) | IFN-γ-increased in T cells co-cultured with DCs exposed to viable tachyzoites or antigenic extract. Oppositely, IFN-γ production triggered after interactions between T cells and macrophages exposed to antigenic extract only. | [147] |
| T cells and dendritic cells | C57BL/6 mice | N. caninum tachyzoites (Nc-1) | In early infection, IL-12 production by conventional and plasmacytoid DCs was increased in mesenteric lymph nodes. Increased proportions and numbers of TCRαβ+CD8+IFN-γ+ lymphocytes were detected, not only in the intestinal cells and lymph nodes, but also in the spleen of the infected mice. |
[148] |
| CD4+ and CD8+ T cells | BALB/c mice | N. caninum tachyzoites (Nc-1) | Most of the anti-CD4 mAb-treated mice and all of the anti-CD4 and anti-CD8 mAbs-treated mice died within 30 dpi. In contrast, 100% of PBS-treated mice and 70% of anti-CD8 mAb-treated mice survived more than 30 days. | [149] |
| CD4+ and CD8+ T cells | Heifers | N. caninum in naturally infected animals | More lymphocytes were observed in the uteri of the seropositive pregnant animals than in the seronegative pregnant animals. CD4+ and to lower extent CD8+ cells were distributed in the endometrium and myometrium of the non-pregnant cows and were sparse in the placentomes of pregnant cows. |
[150] |
| T cells | Bovine mononuclear cells from peripheral blood | N. caninum tachyzoites (Nc-Liv) | Percentages of CD2+ and CD4+ T-cells in PBMC increased after infection in both early and late gestation, Percentages of CD8+ T-cells increased 1–2 wpi at day 70. |
[151] |
| CD4+ and CD8+ T cells | Heifer | N. caninum in naturally infected animals | An infiltration of CD4+ and CD8+ T cells were significantly increased. | [152] |
| CD4+ T cells | Cattle | N. caninum tachyzoites antigen (Nc-1) | The concentration of bovine IFN-γ in supernatant collected from CD4+ T cells stimulated with Neospora antigen fractions was higher than samples incubated with mock. | [71] |
| CD4+ T cells | Cattle | N. caninum tachyzoites water soluble lysate (NcWSA) (Nc-1) | NcWSA was fractionated by HPLC and screened for immune-potency using CD4+ve T cell lines. The approach revealed six target proteins (SAG1 SRS2, GRA2, MIC3, GRA7, and MIC11). |
[153] |
| MHC II+ and CD3+ cells | Bovine fetal tissue | N. caninum tachyzoites (Nc-6) | The immunolabeling of MHC II+ and CD3+ cells in fetal tissues was associated with fetal infection with N. caninum Nc-6 Argentina isolate. | [154] |
| Thymus | BALB/c nu/nu (athymic nude) and BALB/ c (WT) mice |
N. caninum tachyzoites (Japanese isolate JPA1) | All the athymic nude mice died within 28 days after intraperitoneal injection of tachyzoites, whereas all the WT mice survived without exhibiting any clinical signs. Tachyzoites were identified in the uterus and pancreas and later spread to many other organs, and nude mice developed high level of serum IFN-γ and IL-6 as infection proceeded. |
[155] |
| Natural killer T cells | BALB/c mice | N. caninum tachyzoites (Nc-1) | The parasite burden in the brain of mice was promoted by the treatment depletion of NKT in mice. | [156] |
| Natural killer and CD8+ cells | Bovine peripheral blood lymphocytes | N. caninum tachyzoites (Nc-Liv) | Phenotyping of peripheral blood lymphocytes showed a drop in the NK cells at 4–6 dpi, followed by an increase in both NK cells and CD8+ T cells at days 11–15. A whole blood flow cytometric assay showed that CD4+ T cells were the major IFN-γ producing cells, but in the early infection both NK cells and CD8+ T cells contributed to IFN-γ production. |
[157] |
| Peripheral blood mononuclear cells | Cattle | N. caninum tachyzoites N. caninum tachyzoites (Nc-Spain7 and Nc-Spain8) | In vitro stimulation of PBMCs from heifers of both infected groups triggered a significant increase of IFN-γ and to a lower extent IL-4 levels from 6 dpi onwards than non-infected group. | [158] |
| B-cells | C57BL/6(WT) and B-cell−/− µMT mice |
N. caninum tachyzoite and antigen (Nc-1) |
WT mice were resistant to disease, but µMT mice died starting from 29 dpi onwards. Tachyzoite antigen-stimulated spleen cells of both WT and µMT mice infected with N. caninum showed a marked proliferative depression at 10 dpi. At 24 dpi, this immunosuppression was still maintained in µMT mice whereas it was restored in WT mice. Stimulated splenocytes of infected µMT mice secreted significantly less IFN-γ and less IL-10 than corresponding WT splenocytes. |
[159] |