Table 1.

Secreted effectors identified in Toxoplasma gondii.

Name	Location	Functions	Interacting Partner	Mouse Virulence of KO Parasites	Gene Name	Ortholog in Cystoisospora	Ortholog in Sarcocystis	Ortholog in Eimeria	Essentiality Score [26]	NonSyn/Snyn SNP	References
ROP5I/III	PVM	Pseudokinase inhibits IRG coating by preparing Irga6 for phosphorylation by ROP18.	Irga6	Highly avirulent [27,28]	TGME49_308090	Y	Y	Y	n/a	3	[27,28]
ROP18I/II	PVM/ER	Serine-threonine kinase inhibits IRG coating by phosphorylating monomeric Irga6. Suppresses unfolded protein response and antigen presentation. Induces apoptosis in neurons by RTN1-C.	IRGs (preferentially Irga6), ATF6ß, RTN1-C	Slightly reduced, ∆rop18/17 double mutant is highly avirulent [29]	TGME49_205250	Y	Y	Y	0.89	4.5	[30]
GRA7	PVM	Alter the turnover kinetics of Irga6. Activate inflammasome.	Irga6, TRAF6, ASC	Slightly reduced, ∆rop18/gra7 double mutant is highly avirulent [31]	TGME49_203310	N	N	N	1.9	4	[31]
ROP17	PVM	Serine-threonine kinase disassembles polymerized Irgb6.	IRGs (preferentially Irgb6)	Slightly reduced, ∆rop18/17 double mutant is highly avirulent [29]	TGME49_258580	Y	Y	Y	1.29	3.8	[29]
GRA60	PVM	Prevents Irga6 and Irgb10 coating on PVM.	n/a	Slightly reduced [32]	TGME49_204270	N	N	N	-0.59	2.41	[32]
ROP54	PVM	Reduces GBP2 loading on PVM.	n/a	Reduced [33]	TGME49_210370	N	N	N	1.07	1.58	[33]
GRA12	IVN/PVM	Prevents IFNγ-induced parasite destruction.	n/a	Highly avirulent [34]	TGME49_288650	Y	Y	Y	1.75	0.64	[34]
GRA15II	PVM	Activates NF-κB, induce secretion of IL-12 and IL-1ß. Mediates IFNγ-induced PV-lysosome fusion and IRG loading.	TRAF2/TRAF6	No difference [35], more virulent [36]	TGME49_275470	N	N	N	2.33	3.75	[35,37,38]
ROP38	IVN/PVM	Inhibits NF-κB pathway and IL-12 production.	n/a	Reduced [39], no difference [40]	TGME49_242110	Y	Y	Y	n/a	4.5	[41,42]
GRA6	IVN/PVM	Induces CXCL2/CCL2 by activation NFAT4, recruits monocytes/neutrophils, and disseminates parasites.	CAMLG	Reduced [43]	TGME49_275440	N	N	N	1.84	8.25	[43]
GRA25	PV	Induces CCL2 secretion.	n/a	Reduced [44]	TGME49_290700	N	N	N	1.31	3.08	[44]
GRA18	Cytoplasm	Activates ß-catenin and release anti-inflammatory chemokines CCL22 and CCL17.	GSK3/PP2A-B56	Reduced [45]	TGME49_288840	N	N	N	1.66	1.93	[45]
MAG1	PVM/Cytoplasm	Suppresses IL-1ß secretion in macrophages.	n/a	Reduced [46]	TGME49_270240	Y	N	N	1.25	1	[46]
ROP16I/III	Nucleus	Suppresses Th1/M1 response, induces Th2/M2 response. Protects mice from lethal ileitis.	STAT3/5/6	More virulent [47,48]	TGME49_262730	N	N	N	1.11	2.37	[47,48]
GRA28	Nucleus	Induces CCL22 secretion.	n/a	No difference [49]	TGME49_231960	N	N	N	1.48	5.25	[49]
GRA24	Nucleus	Activates p38α MAPK and induces Th1/M1 cytokines and chemokines secretion (e.g., IL-12, IL-6, CCL2, CCL5).	p38α MAPK	No difference [50]	TGME49_230180	N	N	N	2.86	2.69	[50]
GRA16	Nucleus	Interferes p53-dependent apoptosis and inhibits NF-κB pathway (in parasite-free tumor model).	HAUSP, PP2A-B55	Reduced in type II strain but not in type I [51]	TGME49_208830	N	N	N	2.28	3.13	[51]
HCE1/TEEGR	Nucleus	Represses NF-κB-induced gene expression (e.g., IL-6, IL-8, IL-1ß).	E2F	Reduced [52]	TGME49_239010	N	N	N	1.46	5.46	[52,53]
TgIST	Nucleus	Represses IFN-induced gene expression (e.g., IRGs loading).	STAT1/2, NuRD	Highly avirulent [54,55]	TGME49_240060	N	N	N	1.44	5.67	[54,55]
TgNSM	Nucleus	Represses IFN-induced gene expression and necroptosis.	NCoR/SMRT	n/a	TGME49_235140	N	N	N	1.41	6.73	[56]

The table represents the immunomodulatory secreted effectors and their properties. The gene names are based on the ME49 strain. Y in the ortholog section indicates the presence of at least one ortholog in the corresponding genus, and N indicates absence. Orthologs and non-synonymous/synonymous SNP ratios are curated based on the ToxoDB release 53. n/a = data not available.