Fig. 4: Binding of P. vivax-infected reticulocytes to hSFs is NF-kB dependent.

a Left panel: hSFs were cultured in the absence (−) or presence (+) of Bay11-7082 for 1 h and taken up experiments of pooled hEVs, PvEVs or PvEVs2 by hSFs made at 24 or 48 h, as indicated. Mature parasites from two different isolates (1 or 2) were added to pre-stimulated hSFs for 45 min. Bound parasites in 300 cells were counted twice for each condition by two different researchers. Data show mean ± SD (n = 2—hEVs and n = 4—PvEVs). Two-sided, Mann–Whitney test *p = 0.0286 (GraphPad). Source data are provided as a Source Data file. Right panel: phase contrast images of Giemsa-staining hSFs were captured by optical microscopy (×100/1.25 oil). Arrows show P. vivax parasites. Scale bars: 10 µm. Each image represents each independent experiment as indicated. b Spleen model of the physiological role of EVs in P. vivax. Circulating plasma-derived extracellular vesicles from infected cells (PvEVs) enter the microvasculature of the spleen and are uptake by human spleen fibroblasts (hSFs). This event signals NF-kB for translocation to the nucleus and transcription of ICAM-1. After translation of ICAM-1 and expression at the surface of hSFs, infected reticulocytes bind to these cells in a niche rich in reticulocytes (circled) where parasites can invade and multiply. A, arteriole; V, venule.