Microfilariae Trigger Eosinophil Extracellular DNA Traps in a Dectin-1-Dependent Manner

Ehrens, Alexandra; Lenz, Benjamin; Neumann, Anna-Lena; Giarrizzo, Samuela; Reichwald, Julia; Frohberger, Stefan J.; Stamminger, Wiebke; Buerfent, Benedikt C.; Fercoq, Frédéric; Martin, Coralie; Kulke, Daniel; Hoerauf, Achim; Hübner, Marc P.

doi:10.1016/j.celrep.2020.108621

Cited by 39 publications

(46 citation statements)

References 50 publications

(55 reference statements)

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“…Bone marrow from naïve mice were used to generate bone marrow-derived eosinophils as previously described ( 10 ). Therefore, isolated bone marrow was counted using the CASY ® TT- cell counter system and cells were seeded in in Advanced RPMI medium with 20% FBS, 1% penicillin/streptomycin, 0.1% gentamycin, 2.5% HEPES and 1% Glutamax (Thermo Fisher Scientific GmbH, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…Neutrophils and eosinophils also share the feature of extracellular DNA trap cell death (ETosis) formation (8,9). This cell death results in the explosive release of intracellular decondensed DNA that co-localizes with granules containing anti-microbial peptides (10,11). As ETosis in response to migrating helminth parasites combines the trapping of migrating larvae with the direct delivery of effector molecules such as MPO and MBP to this "moving target", it has become a recent focus of research in helminth immunology (10,(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

“…This cell death results in the explosive release of intracellular decondensed DNA that co-localizes with granules containing anti-microbial peptides (10,11). As ETosis in response to migrating helminth parasites combines the trapping of migrating larvae with the direct delivery of effector molecules such as MPO and MBP to this "moving target", it has become a recent focus of research in helminth immunology (10,(12)(13)(14). With regard to neutrophil ETosis (NETosis), Onchocerca volvulus nodules were shown to include DNA trap-releasing neutrophils.…”

Section: Introductionmentioning

confidence: 99%

“…Release of extracellular DNA by eosinophils has been described in several eosinophil-associated diseases ( 9 , 15 ) but only limited information is available on eosinophil ETosis (EETosis) in response to helminths. We showed recently that Litomosoides sigmodontis and Dirofilaria immitis microfilariae induce EETosis in human as well as murine eosinophils, which enabled larval entrapment and facilitated microfilariae clearance ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

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Eosinophils and Neutrophils Eliminate Migrating Strongyloides ratti Larvae at the Site of Infection in the Context of Extracellular DNA Trap Formation

et al. 2021

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Parasitic nematodes such as hookworms actively penetrate the skin of their hosts, encountering skin-resident innate immune cells that represent the host´s first line of defense. Here we use Strongyloides ratti as a model for an intestinal helminth parasite with tissue migrating stages. We show that interception and killing of migrating larvae in mice during a 1st infection occurred predominantly in skin and muscle tissue before larvae migrated via lung and head tissue to the intestine. Inhibition of larval migration was even more efficient in immune mice during a 2nd infection where larvae barely left the site of entry i.e. the foot. Using cell-deficient mice we show that interception in the tissue was predominantly mediated by neutrophils and eosinophils while basophils and mast cells were dispensable in vivo. Likewise, neutrophils and eosinophils inhibited S. ratti L3 motility in vitro in the context of ETosis. Thereby eosinophils were strictly dependent on the presence of anti-S. ratti antibodies while neutrophils inhibited L3 motility as such. Also, MPO and MMP-9 were released by neutrophils in response to L3 alone, but immune plasma further stimulated MPO release in an antibody-dependent manner. In summary, our findings highlight the central role of the skin as first line of defense against helminth parasites in both, innate and adaptive immunity.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Eosinophils and Neutrophils Eliminate Migrating Strongyloides ratti Larvae at the Site of Infection in the Context of Extracellular DNA Trap Formation

et al. 2021

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“…A variety of specific markers could be used to define the origin of the DNA web of MCETs such as NADH-ubiquinone oxidoreductase chain 1 (Nd1) and cytochrome c oxidase subunit 1 (Cox1) as markers of mitochondrial DNA. Moreover, markers mainly glyceraldehyde 3-phosphate dehydrogenase gene (Gapdh) and actin beta (Actb) that are specific for nuclear DNA can be used to identify the nuclear DNA [ 133 ] Investigation of MC TC formed MCETs in dermis of psoriasis plaques showed a colocalization of chymase and DNA suggesting that chymase may be a component of MCETs when they are produced by chymase positive MCs. Our knowledge regarding the biologic role of chymase in MCETs and maintaining its enzymatic activity upon binding to DNA web is poor, and more investigation is needed [ 134 ] Microbial evasion of MCETs The mechanisms by which pathogens aim to evade microbial defense by interrupting the formation and function of MCETs present an interesting topic for further investigations.…”

Section: Unmet Questions: Themes For Further Investigationsmentioning

confidence: 99%

Significance of Mast Cell Formed Extracellular Traps in Microbial Defense

Komi

Kuebler

2021

Clinic Rev Allerg Immunol

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Mast cells (MCs) are critically involved in microbial defense by releasing antimicrobial peptides (such as cathelicidin LL-37 and defensins) and phagocytosis of microbes. In past years, it has become evident that in addition MCs may eliminate invading pathogens by ejection of web-like structures of DNA strands embedded with proteins known together as extracellular traps (ETs). Upon stimulation of resting MCs with various microorganisms, their products (including superantigens and toxins), or synthetic chemicals, MCs become activated and enter into a multistage process that includes disintegration of the nuclear membrane, release of chromatin into the cytoplasm, adhesion of cytoplasmic granules on the emerging DNA web, and ejection of the complex into the extracellular space. This so-called ETosis is often associated with cell death of the producing MC, and the type of stimulus potentially determines the ratio of surviving vs. killed MCs. Comparison of different microorganisms with specific elimination characteristics such as S pyogenes (eliminated by MCs only through extracellular mechanisms), S aureus (removed by phagocytosis), fungi, and parasites has revealed important aspects of MC extracellular trap (MCET) biology. Molecular studies identified that the formation of MCET depends on NADPH oxidase-generated reactive oxygen species (ROS). In this review, we summarize the present state-of-the-art on the biological relevance of MCETosis, and its underlying molecular and cellular mechanisms. We also provide an overview over the techniques used to study the structure and function of MCETs, including electron microscopy and fluorescence microscopy using specific monoclonal antibodies (mAbs) to detect MCET-associated proteins such as tryptase and histones, and cell-impermeant DNA dyes for labeling of extracellular DNA. Comparing the type and biofunction of further MCET decorating proteins with ETs produced by other immune cells may help provide a better insight into MCET biology in the pathogenesis of autoimmune and inflammatory disorders as well as microbial defense.

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Eosinophil: An innate immune cell with anti‐filarial vaccine and biomarker potential

Kwarteng

Mensah

Osei-Poku

2023

Health Science Reports

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Background: Filarial infections continue to pose a great challenge in endemic countries. One of the central goals in the fight against human filarial infections is the development of strategies that will lead to the inhibition of microfilariae (mf) transmission. Keeping mf under a certain threshold within endemic populations will stop transmission and eliminate the infection.Method: A narrative review was carried out to identify the possibilities and limitations of exploring the use of eosinophil responses as an anti-filarial vaccine, and biomarker for the detection of filarial infections. An extensive literature search was performed in online scientific databases including PubMed Central, PubMed, BioMed Central, with the use of predefined search terms.Results: A better understanding of the parasite-host interactions will lead to the development of improved and better treatment or vaccine strategies that could eliminate filariasis as soon as possible. Highlighted in this review is the explorative use of eosinophil-producing CLC/Galectin-10 as a potential biomarker for filarial infections. Also discussed are some genes, and pathways involved in eosinophil recruitments that could be explored for anti-filarial vaccine development. Conclusion:In this short communication, we discuss how eosinophil-regulated genes, pathways, and networks could be critical in providing more information on how reliably a front-line immune player could be exploited for anti-filarial vaccine development and early infection biomarker.

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Microfilariae Trigger Eosinophil Extracellular DNA Traps in a Dectin-1-Dependent Manner

Cited by 39 publications

References 50 publications

Eosinophils and Neutrophils Eliminate Migrating Strongyloides ratti Larvae at the Site of Infection in the Context of Extracellular DNA Trap Formation

Eosinophils and Neutrophils Eliminate Migrating Strongyloides ratti Larvae at the Site of Infection in the Context of Extracellular DNA Trap Formation

Significance of Mast Cell Formed Extracellular Traps in Microbial Defense

Eosinophil: An innate immune cell with anti‐filarial vaccine and biomarker potential

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