Hookworms cause a major neglected tropical disease, occurring after larvae penetrate the host skin. Neutrophils are phagocytes that kill large pathogens by releasing neutrophil extracellular traps (NETs), but whether they target hookworms during skin infection is unknown. Using a murine hookworm, Nippostrongylus brasiliensis, we observed neutrophils being rapidly recruited and deploying NETs around skin-penetrating larvae. Neutrophils depletion or NET inhibition altered larvae behavior and enhanced the number of adult worms following murine infection. Nevertheless, larvae were able to mitigate the effect of NETs by secreting a deoxyribonuclease (Nb-DNase II) to degrade the DNA backbone. Critically, neutrophils were able to kill larvae in vitro, which was enhanced by neutralizing Nb-DNase II. Homologs of Nb-DNase II are present in other nematodes, including the human hookworm, Necator americanus, which also evaded NETs in vitro. These findings highlight the importance of neutrophils in hookworm infection and a potential conserved mechanism of immune evasion.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.chom.2020.01.011 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structure-switchable branched inhibitors regulate the activity of CRISPR-Cas12a for nucleic acid diagnostics.
Anal Chim Acta
January 2025
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, People's Republic of China; Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, People's Republic of China; Hubei Engineering Center for Infectious Disease Prevention, Control and Treatment, Wuhan, People's Republic of China. Electronic address:
Background: In current years, the CRISPR (clustered regularly interspaced short palindromic repeats) based strategies have emerged as the most promising molecular tool in the field of gene editing, intracellular imaging, transcriptional regulation and biosensing. However, the recent CRISPR-based diagnostic technologies still require the incorporation of other amplification strategies (such as polymerase chain reaction) to improve the cis/trans cleavage activity of Cas12a, which complicates the detection workflow and lack of a uniform compatible system to respond to the target in one pot.
Results: To better fully-functioning CRISPR/Cas12a, we reported a novel technique for straightforward nucleic acid detection by incorporating enzyme-responsive steric hindrance-based branched inhibitors with CRISPR/AsCas12a methodology.
A non-covalently bound redox indicator for electrochemical CRISPR-Cas12a and DNase I biosensors.
Anal Chim Acta
January 2025
Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, UT, 84322, USA; Department of Chemistry, University of Louisiana at Lafayette, 300 East St. Mary Blvd, Lafayette, LA, 70504, USA. Electronic address:
A rapid and accurate biosensor for detecting disease biomarkers at point-of-care is essential for early disease diagnosis and preventing pandemics. CRISPR-Cas12a is a promising recognition element for DNA biosensors due to its programmability, specificity, and deoxyribonuclease activity initiated in the presence of a biomarker. The current electrochemical CRISPR-Cas12a-based biosensors utilize the single-stranded DNA (ssDNA) self-assembled on an electrode surface and covalently modified with the redox indicator, usually methylene blue (MB).
View Article and Find Full Text PDFDetection of microRNA-21 based on smartly designed ratiometric electrochemical sensor and dual-signal amplification.
Anal Chim Acta
January 2025
Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, School of Medicine, Linyi University, Linyi, China. Electronic address:
MicroRNA (miRNA) serves as an effective and viable biomarker for early diagnosis and monitoring of cancer disorders. It is highly expressed in tumor cells, including lung cancer, liver cancer and lymphoma. Herein, we propose a ratiometric electrochemical sensor for ultrasensitive detection of miRNA-21 using dual signal amplification, hybridization chain reaction and Exo III assisted-amplification.
View Article and Find Full Text PDFStructural and bioinformatics analyses identify deoxydinucleotide-specific nucleases and their association with genomic islands in gram-positive bacteria.
Nucleic Acids Res
January 2025
CSSB Centre for Structural Systems Biology, Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607 Hamburg, Germany.
Dinucleases of the DEDD superfamily, such as oligoribonuclease, Rexo2 and nanoRNase C, catalyze the essential final step of RNA degradation, the conversion of di- to mononucleotides. The active sites of these enzymes are optimized for substrates that are two nucleotides long, and do not discriminate between RNA and DNA. Here, we identified a novel DEDD subfamily, members of which function as dedicated deoxydinucleases (diDNases) that specifically hydrolyze single-stranded DNA dinucleotides in a sequence-independent manner.
View Article and Find Full Text PDFDesign and in vitro anticancer assessment of a click chemistry-derived dinuclear copper artificial metallo-nuclease.
Nucleic Acids Res
January 2025
School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland.
Copper compounds with artificial metallo-nuclease (AMN) activity are mechanistically unique compared to established metallodrugs. Here, we describe the development of a new dinuclear copper AMN, Cu2-BPL-C6 (BPL-C6 = bis-1,10-phenanthroline-carbon-6), prepared using click chemistry that demonstrates site-specific DNA recognition with low micromolar cleavage activity. The BPL-C6 ligand was designed to force two redox-active copper centres-central for enhancing AMN activity-to bind DNA, via two phenanthroline ligands separated by an aliphatic linker.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!