scholarly journals Efficient Flow Synthesis of Human Antimicrobial Peptides

2020 ◽  
Vol 73 (4) ◽  
pp. 380
Author(s):  
John S. Albin ◽  
Bradley L. Pentelute
Keyword(s):  
Natural Products ◽  
Immune Responses ◽  
Antimicrobial Peptides ◽  
Large Scale ◽  
Flow Chemistry ◽  
Flash Chromatography ◽  
Reverse Phase ◽  
Vast Array ◽  
Host Immune Responses ◽  
Therapeutic Development

Organisms from all kingdoms of life have evolved a vast array of peptidic natural products to defend against microbes. These are known collectively as antimicrobial peptides (AMPs) or host defence peptides, reflecting their abilities not only to directly kill microbes, but also to modulate host immune responses. Despite decades of investigation, AMPs have yet to live up to their promise as lead therapeutics, a reality that reflects, in part, our incomplete understanding of these diverse agents in their various physiological contexts. Towards improving our understanding of AMP biology and the ways in which this can be best leveraged for therapeutic development, we are interested in large-scale comparisons of the antimicrobial and immunological activities of human AMPs, an undertaking that requires an efficient workflow for AMP synthesis and subsequent characterization. We describe here the application of flow chemistry and reverse-phase flash chromatography to the generation of 43AMPs, approaches that, when combined, significantly expedite synthesis and purification, potentially facilitating more systematic approaches to downstream testing and engineering.

scholarly journals Multiomic Immunophenotyping of COVID-19 Patients Reveals Early Infection Trajectories

2020 ◽  
Author(s):  
Yapeng Su ◽  
Daniel Chen ◽  
Christopher Lausted ◽  
Dan Yuan ◽  
Jongchan Choi ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Surface Proteins ◽  
Host Immune Responses ◽  
Therapeutic Development ◽  
Clinical Measures ◽  
Whole Transcriptome

SUMMARYHost immune responses play central roles in controlling SARS-CoV2 infection, yet remain incompletely characterized and understood. Here, we present a comprehensive immune response map spanning 454 proteins and 847 metabolites in plasma integrated with single-cell multi-omic assays of PBMCs in which whole transcriptome, 192 surface proteins, and T and B cell receptor sequence were co-analyzed within the context of clinical measures from 50 COVID19 patient samples. Our study reveals novel cellular subpopulations, such as proliferative exhausted CD8+ and CD4+ T cells, and cytotoxic CD4+ T cells, that may be features of severe COVID-19 infection. We condensed over 1 million immune features into a single immune response axis that independently aligns with many clinical features and is also strongly associated with disease severity. Our study represents an important resource towards understanding the heterogeneous immune responses of COVID-19 patients and may provide key information for informing therapeutic development.

Bacterial Persisters and Infection: Past, Present, and Progressing

2019 ◽  
Vol 73 (1) ◽  
pp. 359-385 ◽  
Author(s):  
Bridget Gollan ◽  
Grzegorz Grabe ◽  
Charlotte Michaux ◽  
Sophie Helaine
Keyword(s):  
Immune Responses ◽  
Environmental Cues ◽  
Antibiotic Exposure ◽  
Scientific Communities ◽  
Clonal Population ◽  
Vast Array ◽  
Host Immune Responses ◽  
History Of ◽  
Harsh Conditions

Persisters are nongrowing, transiently antibiotic-tolerant bacteria within a clonal population of otherwise susceptible cells. Their formation is triggered by environmental cues and involves the main bacterial stress response pathways that allow persisters to survive many harsh conditions, including antibiotic exposure. During infection, bacterial pathogens are exposed to a vast array of stresses in the host and form nongrowing persisters that survive both antibiotics and host immune responses, thereby most likely contributing to the relapse of many infections. While antibiotic persisters have been extensively studied over the last decade, the bulk of the work has focused on how these bacteria survive exposure to drugs in vitro. The ability of persisters to survive their interaction with a host is important yet underinvestigated. In order to tackle the problem of persistence of infections that contribute to the worldwide antibiotic resistance crisis, efforts should be made by scientific communities to understand and merge these two fields of research: antibiotic persisters and host-pathogen interactions. Here we give an overview of the history of the field of antibiotic persistence, report evidence for the importance of persisters in infection, and highlight studies that bridge the two areas.

scholarly journals Acquired immune heterogeneity and its sources in human helminth infection

Parasitology ◽  
2010 ◽  
Vol 138 (2) ◽  
pp. 139-159 ◽  
Author(s):  
C. D. BOURKE ◽  
R. M. MAIZELS ◽  
F. MUTAPI
Keyword(s):  
Immune Responses ◽  
Large Scale ◽  
Antigen Expression ◽  
Epidemiological Studies ◽  
Public Health Importance ◽  
Host Immune Responses ◽  
Parasitic Worm ◽  
Acquired Immune Responses ◽  
The Impact

SUMMARYSimilarities in the immunobiology of different parasitic worm infections indicate that co-evolution of humans and helminths has shaped a common anti-helminth immune response. However, recentin vitroand immuno-epidemiological studies highlight fundamental differences and plasticity within host-helminth interactions. The ‘trade-off’ between immunity and immunopathology inherent in host immune responses occurs on a background of genetic polymorphism, variable exposure patterns and infection history. For the parasite, variation in life-cycle and antigen expression can influence the effector responses directed against them. This is particularly apparent when comparing gastrointestinal and tissue-dwelling helminths. Furthermore, insights into the impact of anti-helminthic treatment and co-infection on acquired immunity suggest that immune heterogeneity arises not from hosts and parasites in isolation, but also from the environment in which immune responses develop. Large-scale differences observed in the epidemiology of human helminthiases are a product of complex host-parasite-environment interactions which, given potential for exposure to parasite antigensin utero, can arise even before a parasite interacts with its human host. This review summarizes key differences identified in human acquired immune responses to nematode and trematode infections of public health importance and explores the factors contributing to these variations.

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.

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