Table 2.

The main proteins of Toxoplasma gondii identified as virulence factors and their interaction with the immune system

Proteins	Source	Virulence mechanisms and immunological importance	References
Rhoptry protein 5 (ROP5)	Rhoptries	Regulation of ROP18 catalytic activity, forming a ROP5/ROP18 complex Blocking of interferon (IFN)-γ-mediated macrophage microbicidal activity Limits antigen presentation in macrophages and dendritic cells	[58, 140]
ROP7		Interacts with the NACHT domain of NLR family pyrin domain-containing 3 (NLRP3) and promotes inflammasome hyperactivation and induction of interleukin (IL)-1β	[66]
ROP16		Phosphorylation of signal transducer and activator of transcription protein 3 (STAT3) and STAT6 and induction of IL-12 and IFN-γ-mediated inflammatory response	[57, 141]
ROP18		Downregulation of the macrophage production of IL-16, TNF-α and IL-12 by phosphorylation of p65 domain of nuclear factor kappa B (NF-κB) Suppression of antigen presentation mechanisms in macrophages and dendritic cells	[57, 142]
GRA3	Dense granules	Regulation of the antigen presentation mechanisms in an IFN-γ or cell-independent manner	[57]
GRA6		Regulation of the activation of nuclear factor of activated T cells 4 (NFAT4) in a strain-specific manner, modulating the expression of C-X-C motif chemokine ligand 2 (CXCL2) and C-C motif chemokine ligand 2 (CCL2) and the recruitment of neutrophils	[76]
GRA7		Interacts with the ROP5/ROP18 complex, binding directly to ROP5 to promote the phosphorylation of immune-regulated guanosine triphosphatase 6 (IRG6) and inactivation of IRG-mediated resistance system	[73]
GRA12		Confers resistance to IFN-γ-mediated immune response, leading to better parasite survival and establishment of infection in a strain-specific manner	[68, 74]
GRA15		Activation of NF-κB via TNF receptor-associated protein 6 (TRAF6) Induction of the inflammasome activation pathway and contributes to IL-1β, IL-12 and TNF-α production	[52, 67, 69]
GRA24		Act as an activator of the immune response, modulating IL-12, IL-1β and TNF-α production via mitogen-activated protein kinase (MAPK) activation and the NF-κB pathway, independently of MYD88 innate immune signal transduction adaptor	[52, 75]
GRA25		Modulation of CCL2 production by macrophages and contributes to efficient parasite survival	[72]