Hepatic amebiasis, predominantly occurring in men, is a focal destruction of the liver due to the invading protozoan Entamoeba histolytica. Classical monocytes as well as testosterone are identified to have important functions for the development of hepatic amebiasis in mice, but a link between testosterone and monocytes has not been identified. Here we show that testosterone treatment induces proinflammatory responses in human and mouse classical monocytes. When treated with 5α-dihydrotestosterone, a strong androgen receptor ligand, human classical monocytes increase CXCL1 production in the presence of Entamoeba histolytica antigens. Moreover, plasma testosterone levels of individuals undergoing transgender procedure correlate positively with the TNF and CXCL1 secretion from their cultured peripheral blood mononuclear cells following lipopolysaccharide stimulation. Finally, testosterone substitution of castrated male mice increases the frequency of TNF/CXCL1-producing classical monocytes during hepatic amebiasis, supporting the hypothesis that the effects of androgens may contribute to an increased risk of developing monocyte-mediated pathologies.

The ability of the parasitePlasmodium falciparumto evade the immune system and be sequestered within human small blood vessels is responsible for severe forms of malaria. The sequestration depends on the interaction between human endothelial receptors andP. falciparumerythrocyte membrane protein 1 (PfEMP1) exposed on the surface of the infected erythrocytes (IEs). In this study, the transcriptomes of parasite populations enriched for parasites that bind to human P-selectin, E-selectin, CD9 and CD151 receptors were analysed. IT4_var02 and IT4_var07 were specifically expressed in IT4 parasite populations enriched for P-selectin-binding parasites; eightvargenes (IT4_var02/07/09/13/17/41/44/64) were specifically expressed in isolate populations enriched for CD9-binding parasites. Interestingly, IT4 parasite populations enriched for E-selectin- and CD151-binding parasites showed identical expression profiles to those of a parasite population exposed to wild-type CHO-745 cells. The same phenomenon was observed for the 3D7 isolate population enriched for binding to P-selectin, E-selectin, CD9 and CD151. This implies that the corresponding ligands for these receptors have either weak binding capacity or do not exist on the IE surface. Conclusively, this work expanded our understanding ofP. falciparumadhesive interactions, through the identification ofvartranscripts that are enriched within the selected parasite populations.

Plasmodium falciparum-infected erythrocytes (PfIEs) present P. falciparum erythrocyte membrane protein 1 proteins (PfEMP1s) on the cell surface, via which they cytoadhere to various endothelial cell receptors (ECRs) on the walls of human blood vessels. This prevents the parasite from passing through the spleen, which would lead to its elimination. Each P. falciparum isolate has about 60 different PfEMP1s acting as ligands, and at least 24 ECRs have been identified as interaction partners. Interestingly, in every parasite genome sequenced to date, at least 75% of the encoded PfEMP1s have a binding domain for the scavenger receptor CD36 widely distributed on host endothelial cells and many other cell types. Here, we discuss why the interaction between PfIEs and CD36 is optimal to maintain a finely regulated equilibrium that allows the parasite to multiply and spread while causing minimal harm to the host in most infections.

In vitro cultivation of Plasmodium falciparum is critical for studying the biology of this parasite. However, it is likely that different in vitro cultivation conditions influence various aspects of the parasite’s life cycle. In the present study two P. falciparum isolates were cultivated using the two most common methods, in which AlbuMAX or human serum as additives are used and the results were compared. The type of cultivation influenced the knob structure of P. falciparum-infected erythrocytes (IEs). IEs cultivated with AlbuMAX had fewer knobs than those cultivated with human serum. Furthermore, knob size varied between isolates and is also depended on the culture medium. In addition, there was a greater reduction in the cytoadhesion of IEs to various endothelial receptors in the presence of AlbuMAX than in the presence of human serum. Surprisingly, cytoadhesion did not correlate with the presence or absence of knobs. Greater numbers of the variant surface antigen families RIFIN, STEVOR and PfMC-2TM were found at the IE membrane when cultivated in the presence of AlbuMAX. Moreover, the type of cultivation had a marked influence on the transcriptome profile. Compared with cultivation with human serum, cultivation with AlbuMAX increased the expression of approximately 500–870 genes.

Plasmodium falciparum, a human malaria parasite, develops in red blood cells (RBCs), which represent approximately 70% of all human blood cells. Additionally, RBC-derived extracellular vesicles (RBC-EVs) represent 7.3% of the total EV population. The roles of microRNAs (miRNAs) in the consequences of P. falciparum infection are unclear. Here, we analyzed the miRNA profiles of non-infected human RBCs (niRBCs), ring-infected RBCs (riRBCs), and trophozoite-infected RBCs (trRBCs), as well as those of EVs secreted from these cells. Hsa-miR-451a was the most abundant miRNA in all RBC and RBC-EV populations, but its expression level was not affected by P. falciparum infection. Overall, the miRNA profiles of RBCs and their EVs were altered significantly after infection. Most of the differentially expressed miRNAs were shared between RBCs and their EVs. A target prediction analysis of the miRNAs revealed the possible identity of the genes targeted by these miRNAs (CXCL10, OAS1, IL7, and CCL5) involved in immunomodulation.

Characterizing the adhesive dynamics of Plasmodium falciparum infected erythrocytes (IEs) to different endothelial cell receptors (ECRs) in flow is a big challenge considering available methods. This study investigated the adhesive dynamics of IEs to five ECRs (CD36, ICAM-1, P-selectin, CD9, CSA) using simulations of in vivo-like flow and febrile conditions. To characterize the interactions between ECRs and knobby and knobless IEs of two laboratory-adapted P. falciplarum isolates, cytoadhesion analysis over time was performed using a new tracking bioinformatics method. The results revealed that IEs performed rolling adhesion exclusively over CD36, but exhibited stationary binding to the other four ECRs. The absence of knobs affected rolling adhesion both with respect to the distance travelled by IEs and their velocity. Knobs played a critical role at febrile temperatures by stabilizing the binding interaction. Our results clearly underline the complexity of the IE-receptor interaction and the importance of knobs for the survival of the parasite at fever temperatures, and lead us to propose a new hypothesis that could open up new strategies for the treatment of malaria.