Splenic Innate B1 B Cell Plasmablasts Produce Sustained Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-3 Cytokines during Murine Malaria Infections Host Response and Inflammation

The physiopathology of malaria, one of the most deadly human parasitic diseases worldwide, is complex, as it is a systemic disease involving multiple parasitic stages and hosts and leads to the activation of numerous immune cells and release of inflammatory mediators. While some cytokines increased in the blood of patients infected with Plasmodium falciparum have been extensively studied, others, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), have not received much attention. GM-CSF and IL-3 belong to the β common (βc/CD131) chain family of cytokines, which exhibit pleiotropic functions, including the regulation of myeloid cell growth, differentiation, and activation. GM-CSF can be secreted by multiple cell types, whereas IL-3 is mostly restricted to T cells, yet innate response activator (IRA) B cells, a subset of innate B1 B cells, also produce significant amounts of these cytokines during bacterial sepsis via Toll-like receptor 4 (TLR4)/MyD88 sensing of lipopolysaccharides. Herein, using murine models of malaria, we report a sustained production of GM-CSF and IL-3 from IgM+ and IgM–/IgG+ CD138+ Blimp-1+ innate B1b B cell plasmablasts. IgM+ B1b B cells include IRA-like and non-IRA B cells and express higher levels of both cytokines than do their IgG+ counterparts. Interestingly, as infection progresses, the relative proportion of IgM+ B1 B cells decreases while that of IgG+ plasmablasts increases, correlating with...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Host Response and Inflammation Source Type: research

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Resistance has developed in Plasmodium malaria parasites to every antimalarial drug in clinical use, prompting the need to characterize the pathways mediating resistance. Here, we report a framework for assessing development of resistance of Plasmodium falciparum to new antimalarial therapeutics. We investigated development of resistance by P. falciparum to the dihydroorotate dehydrogenase (DHODH) inhibitors DSM265 and DSM267 in tissue culture and in a mouse model of P. falciparum infection. We found that resistance to these drugs arose rapidly both in vitro and in vivo. We identified 13 point mutations mediating resistanc...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
In this study, we used focused-ion-beam-milling combined with scanning-electron-microscopy to report the 3D architecture during nuclear segregations in oocyst stage. This advanced technology allowed us to analyse the 3D details of organelle segregation inside the oocyst during sporogony formation. It was revealed that multiple nuclei were involved with several centrosomes in one germ nucleus during sporozoite budding (endopolygeny). Our high-resolution 3D analysis uncovered the endopolygeny-like nuclear architecture of Plasmodium in the definitive host. This nuclear segregation was different from that in the blood stage, a...
Source: Parasitology International - Category: Parasitology Source Type: research
We cover a lot of news and announcements about digital health technologies to provide context for you. Even within The Medical Futurist team, there are favorite technologies and trends. And we thought it would be time to share the technologies we’re excited about! With advancements in exoskeleton technology, A.I.’s ever-increasing importance in healthcare and technologies like 5G and quantum computing soon going mainstream, there’s much to be excited about! Without further ado, let’s jump in! 1. Quantum Computing: faster, cheaper and safer Late last month, Google claimed “quantum suprema...
Source: The Medical Futurist - Category: Information Technology Authors: Tags: Future of Medicine digital health Healthcare technology digital technology Source Type: blogs
We reported three cases of possible parasite resistance to artemether-lumefantrine therapy. All subjects had complete parasite clearance when treated with other antimalarial drugs. This observation necessitates the urgent need to re-evaluate artemether-lumefantrine medication in Nigeria since it is one of the most commonly used ACT drug.
Source: Revista da Sociedade Brasileira de Medicina Tropical - Category: Tropical Medicine Source Type: research
Despite the extensive endeavours, developing an effective malaria vaccine remains as a great challenge. Apical membrane antigen 1 (AMA-1) located on the merozoite surface of parasites belonging to the genus Plasm...
Source: Malaria Journal - Category: Infectious Diseases Authors: Tags: Research Source Type: research
Biannual mass azithromycin administration to preschool children reduces all-cause mortality, but the mechanism for the effect is not understood. Azithromycin has activity against malaria parasites, and malaria...
Source: Malaria Journal - Category: Infectious Diseases Authors: Tags: Research Source Type: research
Treatment for severe malaria must be prompt with effective parenteral antimalarial drugs for at least 24  h to achieve fast parasite clearance, and when the patient can tolerate oral therapy, treatment should b...
Source: BMC Infectious Diseases - Category: Infectious Diseases Authors: Tags: Research article Source Type: research
lli Mosquitoes (Diptera: Culicidae) are vectors of pathogens and parasites of great medical and veterinary relevance. The possible association between mosquitoes, infectious diseases, and cancer has been investigated. Despite its potential importance, there is a severe lack of research data on the topic. Herein, current knowledge, tenuous links, and related challenges on the topic were examined, grouping information under four major hypotheses. The first hypothesis is that the infection of mosquito-vectored parasites, with special reference to Plasmodium spp., may lead to cancer. The International Agency for Research o...
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Benchmark Source Type: research
Plasmodium falciparum malaria is a disease causing high morbidity and mortality rates worldwide, mainly in sub-Saharan Africa. Candidates have been identified for vaccines targeting the parasite’s blood stage; this stage is important in the development of symptoms and clinical complications. However, no vaccine that can directly affect morbidity and mortality rates is currently available. This review analyzes the formulation, methodological design, and results of active clinical trials for merozoite-stage vaccines, regarding their safety profile, immunological response (phase Ia/Ib), and protective efficacy levels (p...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
(University College London) DNA from 75-year old eradicated European malaria parasites uncovers the historical spread of one of the two most common forms of the disease, Plasmodium vivax, from Europe to the Americas during the colonial period, finds a new study co-led by UCL published in Molecular Biology and Evolution.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
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