Table 3.

Toxoplasma gondi impact on NF-κB activity and outcomes.

Parasite	Infection/Life Stage/Antigen	Host/Location/Model	Effect on NF-κB	Outcome
T. gondii [82]	Tachyzoites	Mouse primary peritoneal macrophages	Phosphorylation of p65 through downregulation of miR-187.	Delayed production of IL-12.
T. gondii [87]	Dense granule protein GRA16	Human Non-Small Cell Lung Cancer H1299 cells deficient in p53	GRA16 prevents NF-κB activation; decreased total and nuclear levels of p65, decreased IKKβ level, decreased phosphorylation of IkBα.	Decrease in cell survival, induce cell apoptosis.
T. gondii [86]	Tachyzoites	Human neutrophils	Reduction in LPS-induced IκBα degradation and p65 phosphorylation.	Reduction in release of LPS induced IL-1β.
T. gondii [88]	Tachyzoites of virulent & avirulent strains	In vivo: mice. In vitro: bone marrow derived macrophages, RAW 264.7, adherent peritoneal macrophages, HELA cells	Virulent strain resulted in less p65 translocation to the nucleus and IκBα phosphorylation compared to avirulent strain.	Avirulent strains induced increased TNF-α and IL-12 release compared to virulent strains. Avirulent and virulent strain polarized macrophages towards M1 and M2 phenotypes, respectively.
T. gondii [89]	Tachyzoites of virulent strain	Human foreskin fibroblasts, NIH 3T3 fibroblasts, MEF, HeLa, and COS cell lines, as well as primary cultures of mouse and human macrophages	Lack of nuclear p65/RelA translocation despite IκB degradation. No increase in expression of NF-κB dependent genes upon infection.	The results show that T. gondi may use undefined mechanisms to interfere with NF-κB signaling.
T. gondii [84]	Tachyzoites of virulent strain	Mouse bone marrow-derived macrophages	Inhibition of LPS-induced NF-κB translocation.	Blocked production of proinflammatory TNF-α and delayed (24 h) IL-12 in response to LPS.
T. gondii [81]	Tachyzoites of virulent strain	In vivo: mice. In vitro: mouse bone marrow derived macrophages	In vivo: activation of NF-κB, higher expression of p65, p50 from 24 h. In vitro: no p65 and cRel translocation to nucleus.	In vitro: reduced capacity to increase transcription of IL-12, IL-18, and iNOS in response to LPS and IFN-γ.
T. gondii [90]	in vitro infection	3T3 mouse embryonic fibroblasts, 3T3 p65−/− fibroblasts	nuclear translocation of p50 and p65. Higher affinity to DNA for p50, p52, p65, and RelB. Phosphorylation but no IκB degradation.	Upregulation of antiapoptotic responses.
T. gondii [91]	T. gondi ROP18+ strain T. gondi ROP18− strain	Human foreskin fibroblast, RAW264.7 (mouse macrophage cell line), U937 (human macrophage cell line)	ROP18+ strain induced p65 phosphorylation at Ser468 and promotes its degradation.	ROP18+: reduced LPS-induced IL-6, IL-12, and TNF-α; M2-biased phenotypes. ROP18-: enhanced LPS-induced IL-6, IL-12, and TNF-α; M1-biased activation. This strain has a relative inability to inhibit the NF-κB pathway.
T. gondii [92]	Tachyzoites	Mouse bone marrow-derived macrophages	No change in LPS induced p65 accumulation in nucleus as well as NF-kB binding to DNA. Significant diminished ability of p65 to bind to TNF-α promoter.	Describes T. gondi’s ability to interfere with TNF-α transcription.
T. gondii [74]	Tachyzoites of type I, II and III	Primary human monocytes and THP-1 cells	Type II: increased p65 accumulation in nucleus.	Type II: expression of IL-1β.
T. gondii [85]	Tachyzoites	Primary human peripheral blood monocytes	Increase in phosphorylation of p65.	Expression of IL-1β.
T. gondii [80]	Cysts	Wild type and RelB−/− C57B6 mice.	Infection induces NF-κB DNA binding activities of p65 and RelB containing complexes in the spleen.	RelB−/− mice show high mortality in response to the infection with negligible levels of IFN-γ and diminished NK cell activity.
T. gondii [83]	Tachyzoites	In vivo: Mice (injected intra peritoneally with tachyzoites). In vitro: mouse peritoneal macrophages macrophage cell lines (RAW 264.7 and THP-1)	In vivo: no NF-κB translocation in macrophages or neutrophils within 4h of infection. In vitro: rapid IκB phosphorylation and degradation but NF-κB p50-p65 heterodimers did not translocate to the nucleus.	In vitro: little or no production of IL-12 and TNF-α; LPS triggering unable to promote IL-12 and TNF-α production.