Sex-Linked Differences in Malaria Risk Across the Lifespan.
Current topics in microbiology and immunology
2023; 441: 185-208
Despite the high burden of malaria worldwide, there is surprisingly scarce research on sex-based differences in malaria outside of pregnancy. A more thorough understanding of sexual dimorphism in malaria, and what underlies these sex-based differences, could elucidate the underlying mechanisms driving malaria pathogenesis and has the potential to inform malaria control efforts, including new vaccines. This review summarizes our current understanding of sex-based differences in the epidemiology of malaria across the lifespan, potential sex- or gender-based mechanisms driving these differences, and the knowledge gaps that need to be addressed.
View details for DOI 10.1007/978-3-031-35139-6_7
View details for PubMedID 37695429
View details for PubMedCentralID 4157516
Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria.
Science translational medicine
2023; 15 (680): eadd9012
Natural killer (NK) cells likely play an important role in immunity to malaria, but the effect of repeated malaria on NK cell responses remains unclear. Here, we comprehensively profiled the NK cell response in a cohort of 264 Ugandan children. Repeated malaria exposure was associated with expansion of an atypical, CD56neg population of NK cells that differed transcriptionally, epigenetically, and phenotypically from CD56dim NK cells, including decreased expression of PLZF and the Fc receptor γ-chain, increased histone methylation, and increased protein expression of LAG-3, KIR, and LILRB1. CD56neg NK cells were highly functional and displayed greater antibody-dependent cellular cytotoxicity than CD56dim NK cells. Higher frequencies of CD56neg NK cells were associated with protection against symptomatic malaria and high parasite densities. After marked reductions in malaria transmission, frequencies of these cells rapidly declined, suggesting that continuous exposure to Plasmodium falciparum is required to maintain this modified, adaptive-like NK cell subset.
View details for DOI 10.1126/scitranslmed.add9012
View details for PubMedID 36696483
Type I regulatory T cells in malaria: of mice and men Jason Nideffer, Prasanna Jagannathan
JOURNAL OF CLINICAL INVESTIGATION
2023; 133 (1)
Type I regulatory T (Tr1) cells are a population of regulatory CD4+ T cells implicated in the suppression of pathological immune responses across multiple diseases, but a unifying transcriptional signature of Tr1 identity across disease contexts has not been characterized. In this issue of the JCI, Edward, Ng, and colleagues identified a conserved transcriptional signature that distinguished Tr1 (IL-10+IFN-γ+) from Th1 (IL-10-IFN-γ+) cells in human and mouse malaria. This signature implicated genes encoding inhibitory receptors - including CTLA-4 and LAG-3 - and transcription factors - including cMAF. The authors identified coinhibitory receptor expression that distinguished Tr1 cells from other CD4+ T cell subsets. Furthermore, cMAF - and, to a lesser extent, BLIMP-1 - promoted IL-10 production in human CD4+ T cells. BLIMP-1 also played a role in supporting the expression of inhibitory receptors. These findings describe a few key features that seem to be conserved by Tr1 cells across multiple species, disease contexts, and marker definitions.
View details for DOI 10.1172/JCI166019
View details for Web of Science ID 000992543100002
View details for PubMedID 36594472
View details for PubMedCentralID PMC9797330