Theft of host transferrin receptor-1 by Toxoplasma gondii is required for infection
- 1Department of Molecular Biology, University of Wyoming
- 2Instituto Gulbenkian de Ciência
- 3Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth
Abstract
Host nutrient acquisition is essential for apicomplexan parasite infection, yet mechanisms underpinning this are not defined. We discovered the genome of Toxoplasma gondii lacks conserved genes for iron transport and storage and these host cell proteins, including the transferrin receptor 1, transferrin, ferritin heart/heavy and liver/light chains, and clathrin light chain, are robustly taken up by tachyzoites. Acquisition of these host cell proteins was conserved across host cell species and parasite virulence types. Increased trafficking of host cell transferrin receptor 1 to endolysosomes boosted tachyzoite acquisition of host proteins and growth rate. Bradyzoites possessed little capacity to acquire host cell proteins, consistent with the cyst wall representing a barrier to host cell protein cargo. This study provides insight into essential functions associated with parasite theft of host iron acquisition and storage proteins.
IMPORTANCE: Host nutrient theft is a dogmatic principle of parasitism. The paradigm that Toxoplasma gondii avoids association with host proteins, seemingly abstaining from them as a nutritional stream and for immune system avoidance, is changing. Many host proteins are enriched at the parasitophorous vacuole, but that barrier may be breached since exogenous proteins expressed by host cells transverse to T. gondii bodies. Our work presented here provides in vivo context to this new view because several host iron homeostatic proteins are acquired and retained within the parasite to support infection. These findings not only shed light on how T. gondii could acquire iron but also reveal new host-parasite interactions of theft and integration of host proteins by pathogens.
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BibTeX
@article{denton2026theft,
title = {{Theft of host transferrin receptor-1 by Toxoplasma gondii is required for infection}},
author = {Stephen L. Denton and Alexa Mejia and Lindsay L. Nevarez and Miguel P. Soares and Barbara A. Fox and David J. Bzik and Jason P. Gigley},
journal = {mBio},
year = {2026},
month = oct,
doi = {10.1128/mbio.01248-26},
url = {https://journals.asm.org/doi/10.1128/mbio.01248-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Theft of host transferrin receptor-1 by Toxoplasma gondii is required for infection
AU - Stephen L. Denton
AU - Alexa Mejia
AU - Lindsay L. Nevarez
AU - Miguel P. Soares
AU - Barbara A. Fox
AU - David J. Bzik
AU - Jason P. Gigley
PY - 2026
DA - 2026/10/23
JO - mBio
DO - 10.1128/mbio.01248-26
UR - https://journals.asm.org/doi/10.1128/mbio.01248-26
AB - Host nutrient acquisition is essential for apicomplexan parasite infection, yet mechanisms underpinning this are not defined. We discovered the genome of Toxoplasma gondii lacks conserved genes for iron transport and storage and these host cell proteins, including the transferrin receptor 1, transferrin, ferritin heart/heavy and liver/light chains, and clathrin light chain, are robustly taken up by tachyzoites. Acquisition of these host cell proteins was conserved across host cell species and parasite virulence types. Increased trafficking of host cell transferrin receptor 1 to endolysosomes boosted tachyzoite acquisition of host proteins and growth rate. Bradyzoites possessed little capacity to acquire host cell proteins, consistent with the cyst wall representing a barrier to host cell protein cargo. This study provides insight into essential functions associated with parasite theft of host iron acquisition and storage proteins. IMPORTANCE: Host nutrient theft is a dogmatic principle of parasitism. The paradigm that Toxoplasma gondii avoids association with host proteins, seemingly abstaining from them as a nutritional stream and for immune system avoidance, is changing. Many host proteins are enriched at the parasitophorous vacuole, but that barrier may be breached since exogenous proteins expressed by host cells transverse to T. gondii bodies. Our work presented here provides in vivo context to this new view because several host iron homeostatic proteins are acquired and retained within the parasite to support infection. These findings not only shed light on how T. gondii could acquire iron but also reveal new host-parasite interactions of theft and integration of host proteins by pathogens.
SN - 2150-7511
ER -