Current understanding of the immune potential of B-cell subsets in malarial pathogenesis.

In the past several decades, our understanding of how B cells are generated and what function they perform has continued to advance. It is widely accepted that B-cell subsets play a critical role in mediating immune response. Surprisingly, human and murine malarial infections cause major alterations in the composition of B-cell subsets in both the spleen and periphery. Multiple B-cell subsets are well characterized in murine models following primary and secondary infection, although in human malarial infection, these subsets are not well defined. Furthermore, a rare known function of B cells includes the potential role of regulating the activities of other cells in the body as regulatory cells. Plasmodium infection strongly alters the frequency of these regulatory B cells indicating the immunoregulatory function of B cells in malarial. It is important to note that these subsets, taken together, form the cellular basis of humoral immune responses, allowing protection against a wide array of Plasmodium antigens to be achieved. However, it remains a challenge and an important area of investigation to understand how these B-cell subsets work together to provide protection against Plasmodium infection.

IL-10 Producing Regulatory B Cells Mediated Protection against Murine Malaria Pathogenesis.

Various immune cells are known to participate in combating infection. Regulatory B cells represent a subset of B cells that take part in immunomodulation and control inflammation. The immunoregulatory function of regulatory B cells has been shown in various murine models of several disorders. In this study, a comparable IL-10 competent B-10 cell subset (regulatory B cells) was characterized during lethal and non-lethal infection with malaria parasites using the mouse model. We observed that infection of Balb/c mice with P. yoelii I 7XL was lethal, and a rapid increase in dynamics of IL-10 producing B220+CD5+CD1d+ regulatory B cells over the course of infection was observed. However, animals infected with a less virulent strain of the parasite P. yoelii I7XNL attained complete resistance. It was observed that there is an increase in the population of regulatory B cells with an increase of parasitemia; however, a sudden drop in the frequency of these cells was observed with parasite clearance. Adoptive transfer of regulatory B cells to naïve mice followed by infection results in slow parasite growth and enhancement of survival in P. yoelii 17XL (lethal) infected animals. Adoptively transferred regulatory B cells also resulted in decreased production of pro-inflammatory cytokine (IFN-γ) and enhanced production of anti-inflammatory cytokine (IL-10). It infers that these regulatory B cells may contribute in immune protection by preventing the inflammation associated with disease and inhibiting the parasite growth.

A comprehensive study of epitopes and immune reactivity among Plasmodium species.

BACKGROUND: Malaria is a life-threatening disease caused by protozoan parasite of genus Plasmodium. Various antigenic proteins of Plasmodium are considered as the major targets for the development of an effective vaccine. The aim of the current study was a comprehensive analysis of the experimentally validated epitopes of Plasmodium obtained from various immunoassays. METHODS: Plasmodium species epitopes were prefetched from Immune Epitope Database (IEDB). Species specific classification of available epitopes was done for both human and murine malaria parasites. Further, these T cell and B cell epitopes along with MHC I/II binders of different Plasmodium species were examined to find out their capability to induce IFN-γ and IL-10 using IFNepitope and IL-10 Pred, respectively. RESULTS: The species-specific classification of 6874 unique epitopes resulted in the selection of predominant human and murine Plasmodium species. Further, the attempt was made to analyse the immune reactivity of these epitopes for their ability to induce cytokines namely IFN-γ and IL-10. Total, 2775 epitopes were predicted to possess IFN-γ inducing ability, whereas 1275 epitopes were found to be involved in the induction of IL-10. CONCLUSIONS: This study facilitates the assessment of Plasmodium epitopes and associated proteins as a potential approach to design and develop an epitope-based vaccine. Moreover, the results highlight the epitope-based immunization in malaria to induce a protective immune response.

Mesenchymal Stem Cells: A Novel Therapeutic Approach to Enhance Protective Immunomodulation and Erythropoietic Recovery in Malaria.

Mesenchymal stem cells (MSCs) are self-renewing, multi-potent heterogeneous stem cells that display strong tissue protective and restorative properties by differentiating into cells of the mesodermal lineages. In addition to multi-lineage differentiation capacity, MSCs play important roles in regulating immune responses, inflammation, and tissue regeneration. MSCs play a role in the outcome of the pathogenesis of several infectious diseases. A unique subset of MSCs accumulates in secondary lymphoid organs during malaria disease progression. These MSCs counteract the capacity of malaria parasites to subvert activating co-stimulatory molecules and to regulate expression of negative co-stimulatory molecules on T lymphocytes. Consequently, MSCs have the capacity to restore the functions of CD34+ haematopoietic cells and CD4+ and CD8+ T cells during malaria infection. These observations suggest that cell-based therapeutics for intervention in malaria may be useful in achieving sterile clearance and preventing disease reactivation. In addition, MSCs provide host protection against malaria by reprogramming erythropoiesis through accelerated formation of colony-forming-units-erythroid (CFU-E) cells in the bone marrow. These findings suggest that MSCs are positive regulators of erythropoiesis, making them attractive targets for treatment of malarial anemia. MSC-based therapies, unlike anti-malarial drugs, display therapeutic effects by targeting a large variety of cellular processes rather than a single pathway. In the present review we focus on these recent research findings and discuss clinical applications of MSC-based therapies for malaria.

Rice Transcriptome Analysis Reveals Nitrogen Starvation Modulates Differential Alternative Splicing and Transcript Usage in Various Metabolism-Related Genes.

Nitrogen (N) is crucial for plant growth and development; however, excessive use of N fertilizers cause many problems including environmental damage, degradation of soil fertility, and high cost to the farmers. Therefore, immediate implementation is required to develop N efficient crop varieties. Rice being low nitrogen use efficiency (NUE) and a high demand staple food across the world has become a favorite crop to study the NUE trait. In the current study, we used the publicly available transcriptome data generated from the root and shoot tissues of two rice genotypes IR-64 and Nagina-22 (N-22) under optimum N supply (N+) and chronic N-starvation (N-). A stringent pipeline was applied to detect differentially expressed genes (DEGs), alternatively spliced (DAS) genes, differentially expressed transcripts (DETs) and differential transcript usage (DTU) transcripts in both the varieties and tissues under N+ and N- conditions. The DAS genes and DTU transcripts identified in the study were found to be involved in several metabolic and biosynthesis processes. We suggest alternative splicing (AS) plays an important role in fine-tuning the regulation of metabolic pathways related genes in genotype, tissue, and condition-dependent manner. The current study will help in understanding the transcriptional dynamics of NUE traits in the future.

Mesenchymal stem cells protect against malaria pathogenesis by reprogramming erythropoiesis in the bone marrow.

Malaria remains a major public health problem worldwide. The immune mechanisms that mediate protection against malaria are still unclear. Previously, we reported that mesenchymal stem cells (MSCs) play a critical role in host protection against malaria by altering the dynamic balance of T regulatory cells and effector T cells producing inflammatory cytokines. Here, we report that MSCs reprogram haematopoiesis in primary (bone marrow) and secondary (spleen) lymphoid organs to provide host protection against malaria. Adoptive transfer of MSCs from malaria-infected mice to naïve recipient mice that were subsequently infected with malaria parasites dramatically accelerated the formation of colony-forming units-erythroid cells in the bone marrow. Adoptively transferred MSCs also induced expression of the key erythroid cell differentiation factor GATA-1 in the spleen of recipient animals. Interestingly, we further observed a subtle increase in the CD34+ hematopoietic stem and progenitor cells in lymphoid organs, including spleen and lymph nodes. Infusion of MSCs also enhanced T cell proliferation, resulting in increased numbers of both CD4+ and CD8+ T cells in the spleen. MSCs also inhibited the induction of the negative co-stimulatory receptor programmed death-1 by T cells in recipient animals upon infection with malaria parasites. Taken together, our findings suggest that MSCs play a critical role in host protection against malaria infection by modulating erythropoiesis and lymphopoiesis.