75kDa forPfAMA1, 50kDa forTgAMA1, 30kDa forTgSAG1 and 25kDa forTgGRA7 (Supp. those only seropositive for malaria (coef = 6.27,p= 0.076) in reference with double-negative women (coef = 11.35,p= 0.001). These data suggest that plasma samples containing anti-T. gondiiIgG may contribute reducing the development ofP. falciparumparasites. This study provides insight into the immune dynamics of the co-infection by these two apicomplexans with potential implications for developing cross-protective vaccines and therapies. == Supplementary Information == The online version contains supplementary material available at 10.1038/s41598-025-91803-5. Subject terms:Malaria, Parasitic contamination == Introduction == The apicomplexansPlasmodium falciparum (P.f)andToxoplasma gondii (T.g) remain the causal brokers of two challenging parasitic human infections that affect large populations worldwide1. The harmfulness of both pathogens in a context of peri-natality, particularly in pregnant women, remains a major public health concern2,3. When these parasitic infections occur during pregnancy, the outcomes may be worsened because of hormonal and immunological adaptations aimed at protecting the foetus47. In malaria during pregnancy, the affluent presence ofP.f-infected red blood cells within the intervillous spaces of the placenta is usually associated with severe outcomes such as maternal anaemia, prematurity, or low birth weight810. The infected red blood cells within the placenta produce an inflammatory setting that harms both placenta and foetus11,12. Although congenital malaria rarely occurs, it is secondary to the transplacental transmission ofPlasmodium13,14. A primary contamination withP.ftypically induces an immune response characterized by the production of specific antibodies but the longevity of this immunity may vary considerably depending on the intensity and the duration of the infection15,16. Repeated exposure to the parasite contributes maintaining and reinforcing immunity over time16. However, when staying for a long time in settings where malaria transmission is usually low or absent, immune individuals may experience a gradual decline in antibody levels due to waning immune memory17,18. On its side, congenital toxoplasmosis (CT) occurs in foetuses infected with the protozoanT.g19. The tachyzoite, which is the parasitic form capable of dissemination through the bloodstream, is directly transmitted from the primo-infected mother to the foetus and can cause miscarriage in the early pregnancy period. CT can also lead to progressive cognitive and visual impairments over the years in newborns from primo-infected pregnant women20. The immune antibody response toT.gis known to be robust and persistent. Indeed, the parasite can periodically reactivate from its O-Phospho-L-serine dormant state, characterized by bradyzoites encysted in muscular and cerebral cells, into its circulating tachyzoite form with rapid replication2123. The cyst persistence and antigenic stimulation due to re-infections contribute to the long lasting immune response toT.g24. The immune responses elicited againstP.fandT.gexhibit distinct characteristics shaped by each parasites the unique biology which, in turn, can modulate the hosts immune system susceptibility5,25. Apicomplexan parasites share common biological mechanisms like the host cell invasion process involving the expression of similar proteins at their membrane surfaces26,27. It is the case of the apical membrane antigen (AMA1) protein and the rhoptry neck (RON) proteins complex (Fig.1), particularly the RON2 protein28,29, which combination forms the moving junction and triggers the host cell invasion28,30. BothPfAMA1 andTgAMA1 antigens share structural similarities including a hydrophobic pocket that engage the interaction with the RON2 protein31(Fig.2A). This host cell invasion mechanism is usually well studied among apicomplexans for drug design O-Phospho-L-serine or vaccine strategies32,33. == Fig. 1. == Illustration of the O-Phospho-L-serine lytic asexual life cycle and the mechanisms of host cell invasion of the protozoan parasitesP. falciparumandT. gondii.P.fhost cells include only red blood cells.T.ghost cells include macrophages, dendritic cells, muscle cells, neurons and other human cells. The illustration was created with BioRender.com . == Fig. 2. == Structural similarities betweenPfAMA1 andTgAMA1.A.Illustration of the linear structure ofPfAMA1 andTgAMA1 with the amino-acid positions delimiting the ectodomains.B. Three-dimensional structure ofPfAMA1 (PDB ref 4R19) in dark blue,TgAMA1 (PDB O-Phospho-L-serine ref 2X2Z) in cyan and their superposition using PyMOL software. Discontinuous predicted epitopes are indicated in red forPfAMA1 and orange forTgAMA1. RMSD = 2.63 ; TM-score = 0.86. RMSD compares superpositions of three-dimensional protein structures, atom by atom. The closer this number is usually to 0, the closer is the structural alignment. RMSD has been associated with a protein structure alignment algorithm (TM-align) based on the TM-score77. This algorithm evaluates the quality of the aligned structures: 0.0 < TM-score < 0.30 = random structural similarity; 0.5 < TM-score < 1.00 = significant structural similarity. PlasmodiumandToxoplasmaalso share similar characteristics for the 6-cysteine protein superfamily (Supp. Physique1)3436. The most studied 6-cysteine antigens in malaria, are thePfs48/45 gametocyte-specific antigens37eliciting antibodies that block parasite transmission to the mosquito vector38,39. In toxoplasmosis, the SAG1-related-sequence (SRS) family, including the major surface antigen SAG1, also adopts a 6-cysteine protein folding37,40,41. Experiments using anti-TgSAG1 monoclonal antibody therapy in infected pregnant mice to reduce and prevent the vertical transmission ofT.gto the offspring demonstrated the neutralizing role of these antibodies42. These similarities between structure ZAK and function among apicomplexan proteins raise questions about common. O-Phospho-L-serine
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