Malaria, caused by the protozoan Plasmodium, is a devastating mosquito-borne disease with the potential to affect nearly half the world's population. Despite mounting substantial T and B cell responses, humans fail to efficiently control blood-stage malaria or develop sterilizing immunity to reinfections. Although forkhead box P3 (FOXP3)(+)CD4(+) regulatory T (Treg) cells form a part of these responses, their influence remains disputed and their mode of action is unknown. Here we show that Treg cells expand in both humans and mice in blood-stage malaria and interfere with conventional T helper cell responses and follicular T helper (TFH)-B cell interactions in germinal centers. Mechanistically, Treg cells function in a critical temporal window to impede protective immunity through cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4). Targeting Treg cells or CTLA-4 in this precise window accelerated parasite clearance and generated species-transcending immunity to blood-stage malaria in mice. Our study uncovers a critical mechanism of immunosuppression associated with blood-stage malaria that delays parasite clearance and prevents development of potent adaptive immunity to reinfection. These data also reveal a temporally discrete and potentially therapeutically amenable functional role for Treg cells and CTLA-4 in limiting antimalarial immunity.
Pharmacology, Toxicology and Pharmaceutical Science
2
1%
Other
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Unknown
36
22%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 82. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 February 2026.
All research outputs
#665,348
of 34,638,994 outputs
Outputs from Nature Medicine
#2,338
of 11,631 outputs
Outputs of similar age
#10,321
of 354,979 outputs
Outputs of similar age from Nature Medicine
#25
of 62 outputs
Altmetric has tracked 34,638,994 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,631 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 107.8. This one has done well, scoring higher than 79% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 354,979 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 62 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 59% of its contemporaries.
