Activated Vγδ9Vδ2 (γδ2) T lymphocytes that sense parasite-produced phosphoantigens are expanded in Plasmodium falciparum -infected patients. Although previous studies suggested that γδ2 T cells help control erythrocytic malaria, whether γδ2 T cells recognize infected red blood cells (iRBCs) was uncertain. Here we show that iRBCs stained for the phosphoantigen sensor, butyrophilin 3A1 (BTN3A1). γδ2 T cells formed immune synapses and lysed iRBCs in a contact, phosphoantigen, BTN3A1 and degranulation-dependent manner, killing intracellular parasites. Granulysin released into the synapse lysed iRBCs and delivered death-inducing granzymes to the parasite. All intra-erythrocytic parasites were susceptible, but schizonts were most sensitive. A second protective γδ2 T cell mechanism was identified. In the presence of patient serum, γδ2 T cells phagocytosed and degraded opsonized iRBCs in a CD16-dependent manner, decreasing parasite multiplication. Thus, γδ2 T cells have two ways to control blood stage malaria – γδT cell antigen receptor (TCR)-mediated degranulation and phagocytosis of antibody-coated iRBCs.

Plasmodium vivax causes approximately 100 million clinical malaria cases yearly. The basis of protective immunity is poorly understood and thought to be mediated by antibodies. Cytotoxic CD8 T cells protect against other intracellular parasites by detecting parasite peptides presented by human leukocyte antigen class I on host cells. Cytotoxic CD8 T cells kill parasite-infected mammalian cells and intracellular parasites by releasing their cytotoxic granules. Perforin delivers the antimicrobial peptide granulysin and death-inducing granzymes into the host cell, and granulysin then delivers granzymes into the parasite. Cytotoxic CD8 T cells were thought to have no role against Plasmodium spp. blood stages because red blood cells generally do not express human leukocyte antigen class I. However, P. vivax infects reticulocytes that retain the protein translation machinery. Here we show that P. vivax-infected reticulocytes express human leukocyte antigen class I. Infected patient circulating CD8 T cells highly express cytotoxic proteins and recognize and form immunological synapses with P. vivax-infected reticulocytes in a human leukocyte antigen-dependent manner, releasing their cytotoxic granules to kill both host cell and intracellular parasite, preventing reinvasion. P. vivax-infected reticulocytes and parasite killing is perforin independent, but depends on granulysin, which generally efficiently forms pores only in microbial membranes. We find that P. vivax depletes cholesterol from the P. vivax-infected reticulocyte cell membrane, rendering it granulysin-susceptible. This unexpected T cell defense might be mobilized to improve P. vivax vaccine efficacy.

Background and Purpose— Flow diverter technology improvements are necessary to provide safe and good results and enable the treatment of a larger variety of aneurysms. We report a nationwide experience with the Derivo Embolization Device in the treatment of intracranial aneurysms. Methods— BRAIDED (Brazilian Registry of Aneurysms Assigned to Intervention With the Derivo Embolization Device) is a multicenter, prospective, interventional, single-arm trial of the Derivo Embolization Device for the treatment of intracranial aneurysms. The primary effectiveness end point was total aneurysm occlusion at 6- and 12-month angiographies. The secondary safety end point was the absence of serious adverse events during follow-up. Univariable and multivariable logistic regression was performed to identify predictors of aneurysm persistence, periprocedural complications, and adverse events during follow-up. Results— Between December 2016 and October 2018, 146 patients harboring 183 intracranial aneurysms were treated in 151 interventions at 7 centers. Derivo Embolization Device placement was technically successful in all patients. Most aneurysms (86.9%) were located at the internal carotid artery, and the mean diameter was 6.7 mm. At 6 months, 113 of 140 (80.7%) aneurysms met the study’s primary end point, and 74 of 83 (89.2%) met the study’s primary end point at 12 months. Saccular morphology of the aneurysm (odds ratio, 5.66; 95% CI, 1.01–31.77) and the presence of a branch arising from the sac (odds ratio, 6.36; 95% CI, 2.11–22.36) predicted persistence. A long duration of follow-up (odds ratio, 0.86; 95% CI, 0.78–0.95) predicted total occlusion. Of the 146 enrolled patients, 138 (94.5%) were treated without serious adverse events during follow-up. In the multivariable analysis, aneurysms located at a sidewall were less likely to experience these events than those located at bifurcations (odds ratio, 0.07; 95% CI, 0.01–0.51). Conclusions— The Derivo Embolization Device is a safe and effective treatment for intracranial aneurysms. Clinical Trial Registration— URL: http://plataformabrasil.saude.gov.br/login.jsf . Unique identifier: CAAE 77089717.7.1001.5125.

Pulsatile tinnitus of vascular origin may arise in arterial or venous structures. Many authors have reported the association of pulsatile tinnitus with anomalies of dural venous sinuses and the jugular bulb. In such circumstances, mainly concomitantly with disabling tinnitus, endovascular treatment has been successfully employed. We describe here a new case of jugular bulb diverticulum associated with transverse sigmoid sinus stenosis, in a patient presenting with disabling pulsatile tinnitus. She was treated with dural sinus stenting and selective embolization of the diverticulum. In addition, we performed a literature review aiming to identify possible risk factors for developing the symptoms, as well as the safety and results of endovascular treatment.