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The effect of sex on the prevalence and severity of parasitic diseases is an emerging area of research. Several factors underlie sex-based differences, including sociocultural influences that affect exposure to parasites, and physiological disparities linked to biological sex. Hence, human studies must be interpreted cautiously; however, studies conducted under controlled laboratory conditions are important to validate findings in humans. Such research can more effectively elucidate the role of sex-determining physiological factors (particularly their impact on immune responses), as well as the role of sex-specific differences in resistance to, or severity of, parasitic diseases. This review focuses on the overarching impact of biological sex variables on immunity. Both human and rodent experimental data are discussed, with a focus on selected protozoan and helminth infections., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Recently, two genes involved in amoebic liver abscess formation in a mouse model were identified by their differential expression of non-pathogenic (A1np) and pathogenic (B2p) clones of the Entamoeba histolytica isolate HM:1-IMSS. While overexpression of a gene encoding the metallopeptidase EhMP8-2 reduces the virulence of the pathogenic clone B2p, overexpression of the gene ehi_127670 (ehhp127), encoding a hypothetical protein, increases the virulence of the non-pathogenic clone A1np, while silencing this gene in the pathogenic B2p reduces virulence. To understand the role of both molecules in determining the pathogenicity of E. histolytica, silencing, and overexpression transfectants were characterized in detail. Silencing of ehmp8-2, of the homologous gene ehmp8-1, or both in non-pathogenic A1np trophozoites significantly altered the transcript levels of 347, 216, and 58 genes, respectively. This strong change in the expression profiles caused by the silencing of ehmp8-1 and ehmp8-2 implies that these peptidases regulate the expression of numerous genes. Consequently, numerous phenotypic characteristics, including cytopathic, hemolytic, and cysteine peptidase activity, were altered in response to their silencing. Silencing of ehhp127 in pathogenic B2p trophozoites did not affect the expression of other genes, whereas its overexpression in non-pathogenic A1np trophozoites results in an altered expression of approximately 140 genes. EhHP127 is important for trophozoite motility, as its silencing reduces, while its overexpression enhances movement activity. Interestingly, the specific silencing of ehhp127 also significantly affects cytopathic, cysteine peptidase, and hemolytic activities. All three molecules characterized in this study, namely EhMP8-1, EhMP8-2, and EhHP127, are present in amoeba vesicles. The results show that ehmp8-2 and ehhp127 are not only differentially expressed between pathogenic and non-pathogenic amoebae, but that they also significantly affect amoeba pathogenicity-associated phenotypes by completely different mechanisms. This observation suggests that the regulation of amoeba pathogenicity is achieved by a complex network of molecular mechanisms rather than by single factors., Competing Interests: The authors have declared that no competing interest exist., (Copyright: © 2023 Anders et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Differences in immune response between men and women may influence the outcome of infectious diseases. Intestinal infection with Entamoeba histolytica leads to hepatic amebiasis, which is more common in males. Previously, we reported that innate immune cells contribute to liver damage in males in the murine model for hepatic amebiasis. Here, we focused on the influences of sex and androgens on neutrophils in particular. Infection associated with neutrophil accumulation in the liver was higher in male than in female mice and further increased after testosterone treatment in both sexes. Compared with female neutrophils, male neutrophils exhibit a more immature and less activated status, as evidenced by a lower proinflammatory N1-like phenotype and deconvolution, decreased gene expression of type I and type II interferon stimulated genes (ISGs) as well as downregulation of signaling pathways related to neutrophil activation. Neutrophils from females showed higher protein expression of the type I ISG viperin/RSAD2 during infection, which decreased by testosterone substitution. Moreover, ex vivo stimulation of human neutrophils revealed lower production of RSAD2 in neutrophils from men compared with women. These findings indicate that sex-specific effects on neutrophil physiology associated with maturation and type I IFN responsiveness might be important in the outcome of hepatic amebiasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Er-Lukowiak, Hänzelmann, Rothe, Moamenpour, Hausmann, Khatri, Hansen, Boldt, Bärreiter, Honecker, Bea, Groneberg, Fehling, Marggraff, Cadar, Bonn, Sellau and Lotter.)

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., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

The human protozoan parasite Entamoeba histolytica can live in the human intestine for months or years without generating any symptoms in the host. For unknown reasons, amoebae can suddenly destroy the intestinal mucosa and become invasive. This can lead to amoebic colitis or extraintestinal amoebiasis whereby the amoebae spread to other organs via the blood vessels, most commonly the liver where abscesses develop. Entamoeba nuttalli is the closest genetic relative of E. histolytica and is found in wild macaques. Another close relative is E. dispar , which asyptomatically infects the human intestine. Although all three species are closely related, only E. histolytica and E. nuttalli are able to penetrate their host's intestinal epithelium. Lineage-specific genes and gene families may hold the key to understanding differences in virulence among species. Here we discuss those genes found in E. histolytica that have relatives in only one or neither of its sister species, with particular focus on the peptidase, AIG, Ariel, and BspA families., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 König, Honecker, Wilson, Weedall, Hall, Roeder, Metwally and Bruchhaus.)