Background: Co-infection with malaria and intestinal parasites such asAscaris lumbricoidesis common. Malaria parasites induce a pro-inflammatory immune response that contributes to the pathogenic sequelae, such as malarial anaemia, that occur in malaria infection.Ascarisis known to create an anti-inflammatory immune environment which could, in theory, counteract the anti-malarial inflammatory immune response, minimizing the severity of malarial anaemia. This study examined whetherAscarisco-infection can minimize the severity of malarial anaemia.Methods: Data from a randomized controlled trial on the effect of antihelminthic treatment in Nigerian preschool-aged (6–59 months) children conducted in 2006–2007 were analysed to examine the effect of malaria andAscarisco-infection on anaemia severity. Children were enrolled and tested for malaria, helminths and anaemia at baseline, four, and eight months. Six hundred and ninety subjects were analysed in this study. Generalized linear mixed models were used to assess the relationship between infection status andAscarisandPlasmodiumparasite intensity on severity of anaemia, defined as a haemoglobin less than 11 g/dL.Results: Malaria prevalence ranged from 35-78% over the course of this study. Of the malaria-infected children, 55% were co-infected withAscarisat baseline, 60% were co-infected four months later and 48% were co-infected eight months later, underlining the persistent prevalence of malaria-nematode co-infections in this population. Over the course of the study the percentage of anaemic subjects in the population ranged between 84% at baseline and 77% at the eight-month time point. The odds of being anaemic were four to five times higher in children infected with malaria compared to those without malaria.Ascarisinfection alone did not increase the odds of being anaemic, indicating that malaria was the main cause of anaemia in this population. There was no significant difference in the severity of anaemia between children singly infected with malaria and co-infected with malaria andAscaris.Conclusion: In this cohort of Nigerian preschool children, malaria infection was the major contributor to anaemia status.Ascarisco-infection neither exacerbated nor ameliorated the severity of malarial anaemia.

CD4⁺ follicular helper T (Tfh) cells play a vital role in providing help for B cells undergoing selection and differentiation into activated antibody-secreting cells in mammalian germinal centers (GCs). Increasing evidence suggests that Tfh cells are a heterogeneous population that generates cytokine-skewed immune responses - a reflection of the microenvironment during differentiation. This has important ramifications for Tfh-mediated B cell help. Because Tfh subsets can have opposing effects on GC B cell responses, we discuss current findings regarding the differentiation and functions of cytokine-skewed Tfh cells in modulating GC B cell differentiation. Antibodies are important weapons against infectious diseases but can also be pathogenic mediators in some autoimmune conditions. Since cytokine-skewed Tfh cells can influence the magnitude and quality of the humoral response, we address the roles of cytokine-skewed Tfh cells in disease.

Eph receptors are the largest family of receptor tyrosine kinases and mediate a myriad of essential processes in humans from embryonic development to adult tissue homeostasis through interactions with membrane-bound ephrin ligands. The ubiquitous expression of Eph receptors and ephrin ligands among the cellular players of the immune system underscores the importance of these molecules in orchestrating an optimal immune response. This review provides an overview of the various roles of Eph receptors and ephrin ligands in immune cell development, activation, and migration. We also discuss the role of Eph receptors in disease pathogenesis as well as the implications of Eph receptors as future immunotherapy targets. Given the diverse and critical roles of Eph receptors and ephrin ligands throughout the immune system during both resting and activated states, this review aims to highlight the critical yet underappreciated roles of this family of signaling molecules in the immune system.

Infection with the malaria parasite, Plasmodium, is characterized by excessive inflammation. The establishment of a precise balance between the pro- and anti-inflammatory responses is critical to guarantee control of the parasite and survival of the host. IL-10, a key regulatory cytokine produced by many cells of the immune system, has been shown to protect mice against pathology during acute Plasmodium0 chabaudi chabaudi AS model of malaria. However, the critical cellular source of IL-10 is still unknown. In this article, we demonstrate that T cell-derived IL-10 is necessary for the control of pathology during acute malaria, as mice bearing specific deletion of Il10 in T cells fully reproduce the phenotype observed in Il10^−/− mice, with significant weight loss, decline in temperature, and increased mortality. Furthermore, we show that IFN-γ⁺ Th1 cells are the main producers of IL-10 throughout acute infection, expressing high levels of CD44 and ICOS, and low levels of CD127. Although Foxp3⁺ regulatory CD4⁺ T cells produce IL-10 during infection, highly activated IFN-γ⁺ Th1 cells were shown to be the essential and sufficient source of IL-10 to guarantee protection against severe immune-mediated pathology. Finally, in this model of malaria, we demonstrate that the generation of protective IL10⁺IFN-γ⁺ Th1 cells is dependent on IL-27 signaling and independent of IL-21.