scholarly journals Biosynthetic heme of malaria parasite induces cerebral pathogenesis by regulating hemozoin formation and griseofulvin can prevent cerebral malaria

2021 ◽  
Author(s):  
Manjunatha Chandana ◽  
Aditya Anand ◽  
Sourav Ghosh ◽  
Subhashree Beura ◽  
Sarita Jena ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cerebral Malaria ◽  
Severe Malaria ◽  
Malaria Parasite ◽  
Biosynthetic Pathway ◽  
Therapeutic Option ◽  
Food Vacuole ◽  
Host Immune Responses ◽  
Food Vacuoles ◽  
Lipid Unsaturation

ABSTRACTHeme-biosynthetic pathway of malaria parasite is dispensable for asexual stages, but essential for sexual and liver stages. Despite having backup mechanisms to acquire hemoglobin-heme, pathway intermediates and/or enzymes from the host, asexual parasites express heme pathway enzymes and synthesize heme. Here we show heme synthesized in asexual stages promotes cerebral pathogenesis by enhancing hemozoin formation. Hemozoin is a parasite molecule associated with inflammation, aberrant host-immune responses, disease severity and cerebral pathogenesis. The heme pathway knockout parasites synthesize less hemozoin, and mice infected with knockout parasites are completely protected from cerebral malaria and death due to anaemia is delayed. Biosynthetic heme regulates food vacuole integrity and the food vacuoles from knockout parasites are compromised in pH, lipid unsaturation and proteins, essential for hemozoin formation. Targeting parasite heme synthesis by griseofulvin - a FDA-approved drug, prevents cerebral malaria in mice and provides a new adjunct therapeutic option for cerebral and severe malaria.

Pro- and anti-inflammatory immune response profiling prevents severe malaria among Nigerians infected with Plasmodium falciparum: the future for malaria vaccines and therapeutics.

2020 ◽  
Author(s):  
DANIEL OSAGIE OKPOKOR ◽  
ASAGA MAC PETER ◽  
Ajibaye Olusola ◽  
Anthony Danaan Dakul
Keyword(s):  
Plasmodium Falciparum ◽  
Immune Responses ◽  
Severe Malaria ◽  
Inflammatory Cytokines ◽  
Parasite Density ◽  
Malaria Parasite ◽  
World Health ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Background Available evidence indicates that the various stages of the malaria parasite life cycle have specific immune responses. The pro-inflammatory cytokines tend to play an important role in preventing malaria and killing the parasites. Furthermore, the relative levels of pro-and anti-inflammatory cytokines are essential mediators of malaria anemia production and outcomes. Natural human immune responses to malaria recognize extracellular sporozoites and merozoites, both of which have surface-exposed antigens, and which are currently being developed for various vaccines. Methods A total of four hundred sixty- two (462) participants were tested for Plasmodium falciparum. The procedure employed were parasite staining using World Health Organization parasitology laboratory protocol [Microscopy] of Giemsa staining and Enzyme linked immunosorbent assay [ELISA]. Results The subjects in this study showed high levels of INF-γ and TNF-α which decreases with increased malaria severity and high parasite density. These results suggest that INF-γ cytokine and TNF-α may contribute to protection against severe malaria anaemia and parasite clearance. Conversely, infected participants showed higher levels of IL-10, which decreases with severe malaria parasite, furthermore IL-10 levels correlated with parasite density. These findings suggest that higher levels of anti-inflammatory cytokines, especially IL-10 levels may contribute to pathogenesis of complicated malaria by inhibiting the INF-γ and TNF-α production. Conclusion Molecular biological and other serological analysis are needed to elucidate the implication of these cytokines and other pro-inflammatory cytokines as IL-17, IL-21 and IL-22 in the responses to malaria and consequently their involvement in malaria vaccine construct/development as well as other therapeutics for the treatment and elimination of the malaria parasite in our environment.

scholarly journals Maladjusted Host Immune Responses Induce Experimental Cerebral Malaria-Like Pathology in a Murine Borrelia and Plasmodium Co-Infection Model

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e103295 ◽  
Author(s):  
Johan Normark ◽  
Maria Nelson ◽  
Patrik Engström ◽  
Marie Andersson ◽  
Rafael Björk ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cerebral Malaria ◽  
Infection Model ◽  
Experimental Cerebral Malaria ◽  
Host Immune Responses

Role of convalescent plasma therapy in new Coronavirus disease (nCOVID-19): A review

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 546-549
Author(s):  
Shweta Dadarao Parwe ◽  
Milind Abhimanyu Nisargandha ◽  
Rishikesh Thakre
Keyword(s):  
Clinical Trial ◽  
Immune Responses ◽  
Indian Population ◽  
Preventive Treatment ◽  
The Body ◽  
Therapeutic Antibodies ◽  
Plasma Therapy ◽  
Host Immune Responses ◽  
Transparent Liquid

Hitherto, there is no proper line of treatment for the new (nCOVID19). The development of unique antiviral drugs has taken precedence. Therapeutic antibodies () will be a significantly beneficial agent against nCOVID-19. Here the host immune responses to new discussed in this review provide strategy and further treatment and understanding of clinical interventions against nCOVID-19. Plasma therapy uses the antibodies found in the blood of people recovering (or convalesced) from an infection to treat infected patients. When an infection occurs, the body begins producing proteins specially made to kill the germ, called antibodies. Those antibodies coat specifically plasma in the blood of survivors, the yellow transparent liquid blood portion for months or even years. research assesses plasma use from Convalescent patients of infected with nCOVID-19 as a possible preventive treatment. But it is not yet recommended as a line of treatment, and it is used as a clinical trial in the new in Indian population.

scholarly journals Evaluation of dsRNA delivery methods for targeting macrophage migration inhibitory factor MIF in RNAi-based aphid control

2021 ◽  
Author(s):  
Shaoshuai Liu ◽  
Maria Jose Ladera-Carmona ◽  
Minna M. Poranen ◽  
Aart J. E. van Bel ◽  
Karl-Heinz Kogel ◽  
...  
Keyword(s):  
Immune Responses ◽  
Artificial Diet ◽  
Sieve Tube ◽  
Feeding Strategies ◽  
Macrophage Migration ◽  
Delivery Methods ◽  
Host Immune Responses ◽  
Aphid Control ◽  
Barley Leaves ◽  
Sieve Tubes

AbstractMacrophage migration inhibitory factors (MIFs) are multifunctional proteins regulating major processes in mammals, including activation of innate immune responses. In invertebrates, MIF proteins participate in the modulation of host immune responses when secreted by parasitic organisms, such as aphids. In this study, we assessed the possibility to use MIF genes as targets for RNA interference (RNAi)-based control of the grain aphid Sitobion avenae (Sa) on barley (Hordeum vulgare). When nymphs were fed on artificial diet containing double-stranded (ds)RNAs (SaMIF-dsRNAs) that target sequences of the three MIF genes SaMIF1, SaMIF2 and SaMIF3, they showed higher mortality rates and these rates correlated with reduced MIF transcript levels as compared to the aphids feeding on artificial diet containing a control dsRNA (GFP-dsRNA). Comparison of different feeding strategies showed that nymphs’ survival was not altered when they fed from barley seedlings sprayed with naked SaMIF-dsRNAs, suggesting they did not effectively take up dsRNA from the sieve tubes of these plants. Furthermore, aphids’ survival was also not affected when the nymphs fed on leaves supplied with dsRNA via basal cut ends of barley leaves. Consistent with this finding, the use of sieve tube-specific YFP-labeled Arabidopsis reporter lines confirmed that fluorescent 21 nt dsRNACy3, when supplied via petioles or spraying, co-localized with xylem structures, but not with phloem tissue. Our results suggest that MIF genes are a potential target for insect control and also imply that application of naked dsRNA to plants for aphid control is inefficient. More efforts should be put into the development of effective dsRNA formulations.

scholarly journals Dysregulated Immune Responses by ASK1 Deficiency Alter Epithelial Progenitor Cell Fate and Accelerate Metaplasia Development during H. pylori Infection

2020 ◽  
Vol 8 (12) ◽  
pp. 1995
Author(s):  
Yoku Hayakawa ◽  
Yoshihiro Hirata ◽  
Masahiro Hata ◽  
Mayo Tsuboi ◽  
Yukiko Oya ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Cell Fate ◽  
Knockout Mice ◽  
Suppressor Cells ◽  
Inflammatory Cells ◽  
Immune Disorder ◽  
Host Immune Responses ◽  
Epithelial Homeostasis ◽  
H Pylori

The mechanism of H. pylori-induced atrophy and metaplasia has not been fully understood. Here, we demonstrate the novel role of Apoptosis signal-regulating kinase 1 (ASK1) and downstream MAPKs as a regulator of host immune responses and epithelial maintenance against H. pylori infection. ASK1 gene deficiency resulted in enhanced inflammation with numerous inflammatory cells including Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) recruited into the infected stomach. Increase of IL-1β release from apoptotic macrophages and enhancement of TH1-polarized immune responses caused STAT1 and NF-κB activation in epithelial cells in ASK1 knockout mice. Dysregulated immune and epithelial activation in ASK1 knockout mice led to dramatic expansion of gastric progenitor cells and massive metaplasia development. Bone marrow transplantation experiments revealed that ASK1 in inflammatory cells is critical for inducing immune disorder and metaplastic changes in epithelium, while ASK1 in epithelial cells regulates cell proliferation in stem/progenitor zone without changes in inflammation and differentiation. These results suggest that H. pylori-induced immune cells may regulate epithelial homeostasis and cell fate as an inflammatory niche via ASK1 signaling.

scholarly journals Role of Alternative Splicing in Regulating Host Response to Viral Infection

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1720
Author(s):  
Kuo-Chieh Liao ◽  
Mariano A. Garcia-Blanco
Keyword(s):  
Innate Immunity ◽  
Alternative Splicing ◽  
Immune Responses ◽  
Viral Infection ◽  
Rna Splicing ◽  
Type I ◽  
Host Immune Responses ◽  
Transcriptional Regulatory Mechanisms ◽  
Host Virus Interactions

The importance of transcriptional regulation of host genes in innate immunity against viral infection has been widely recognized. More recently, post-transcriptional regulatory mechanisms have gained appreciation as an additional and important layer of regulation to fine-tune host immune responses. Here, we review the functional significance of alternative splicing in innate immune responses to viral infection. We describe how several central components of the Type I and III interferon pathways encode spliced isoforms to regulate IFN activation and function. Additionally, the functional roles of splicing factors and modulators in antiviral immunity are discussed. Lastly, we discuss how cell death pathways are regulated by alternative splicing as well as the potential role of this regulation on host immunity and viral infection. Altogether, these studies highlight the importance of RNA splicing in regulating host–virus interactions and suggest a role in downregulating antiviral innate immunity; this may be critical to prevent pathological inflammation.

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