Secreted filarial nematode galectins modulate host immune cells

Loghry, Hannah J.; Sondjaja, Noelle A; Minkler, Sarah; Kimber, Michael J.

doi:10.3389/fimmu.2022.952104

Cited by 9 publications

(5 citation statements)

References 91 publications

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“…These include galectin (Bm4277), 14-3-3 like protein (Bm4259a), and triosephophate isomerase (Bm13880). More recent work shows that galectin contained in EV could play a role in modulating the host immunodulatory response (Loghry et al, 2022b). In another study, B. malayi Mf EV were isolated with the ExoQuick kit, which allowed us the most direct comparison of results (Ricciardi et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarker candidates for filarial parasite infections by analysis of extracellular vesicles

Yates,

Di Maggio,

Rosa

et al. 2023

Front. Parasitol.

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BackgroundImproved diagnostic tools are needed for detecting active filarial infections in humans. Tests are available that detect adult W. bancrofti circulating filarial antigen, but there are no sensitive and specific biomarker tests for brugian filariasis or loiasis. Here we explored whether extracellular vesicles released by filarial parasites contain diagnostic biomarker candidates.MethodsVesicles were isolated using VN96-affinity purification from supernatants of short-term in vitro cultured B. malayi microfilariae (Mf) and analyzed by mass spectrometry (Bruker timsTOF). Parasite-specific proteins were identified by bioinformatic analysis and a protein was called present if supported by ≥ 2 spectra. After validation with cultures parasites, this approach was then used to analyze vesicles isolated from plasma of animals infected with B. malayi and from humans with heavy Loa loa infections.ResultsVesicles from Mf cultures contained more than 300 B. malayi proteins with high consistency across biological replicates. These included the known Mf excretory antigen BmR1 (AF225296). Over 150 B. malayi proteins were detected in vesicles isolated from plasma samples from two infected animals. Vesicles isolated from plasma from 10 persons with high L. loa Mf densities contained consistently 21 proteins, 9 of them were supported by at least 5 unique peptides and 7 with spectral counts above 10. The protein EN70_10600 (an orthologue of the B. malayi antigen BmR1, GenBank AF225296) was detected in all 10 samples with a total count of 91 spectra and a paralogue (EN70_10598) was detected in 6 samples with a total of 44 spectra.DiscussionExtracellular vesicles released by filarial parasites in vitro and in vivo contain parasite proteins which can be reliably detected by mass spectrometry. This research provides the foundation to develop antigen detection assays to improve diagnosis of active filarial infections in humans.

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Section: Discussionmentioning

confidence: 99%

Identification of biomarker candidates for filarial parasite infections by analysis of extracellular vesicles

Yates,

Di Maggio,

Rosa

et al. 2023

Front. Parasitol.

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“…It produces a galectin that inhibits mast cell degranulation [81]. Galectins are the main extracellular molecules that bind glycans [79] and they influence the outcome of several different nematode infections [79,119]. Both vertebrates and invertebrates produce galectins but although structurally similar they do not appear to be descended from a common ancestor [120].…”

Section: Immunomodulationmentioning

confidence: 99%

The Immune Response to Nematode Infection

Stear

Preston

Piedrafita

et al. 2023

IJMS

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Nematode infection is a major threat to the health of humans, domestic animals and wildlife. Nematodes vary in their effect on the host and in the mechanisms underlying immunity but the general features are becoming clear. There is considerable variation among individuals in resistance to infection and much of this variation is due to genetic variation in the immune response. The major histocompatibility complex has a strong influence on resistance to infection but other genes are collectively more important. Resistant individuals produce more IgA, eosinophils, IgE and mast cells than susceptible individuals and this is a consequence of stronger type 2 (Th2) immune responses. A variety of factors promote Th2 responses including genetic background, diet, molecules produced by the parasite and the location of the infection. A variety of cells and molecules including proteins, glycolipids and RNA act in concert to promote responses and to regulate the response. Nematodes themselves also modulate the host response and over 20 parasite-derived immunomodulatory molecules have been identified. Different species of nematodes modulate the immune response in different ways and probably use multiple molecules. The reasons for this are unclear and the interactions among immunomodulators have still to be investigated.

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“…as well as in other parasitic helminths [17,27,28]. Moreover, enolase has already been proposed as a vaccine candidate against Ascaris suum [62], while galectins are involved in the initiation of the host immune response [35,[63][64][65].…”

Section: Immunoproteomicsmentioning

confidence: 99%

Progresses and challenges in Strongyloides spp. proteomics

Tiberti,

Manfredi,

Piubelli

et al. 2023

Phil. Trans. R. Soc. B

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The availability of high-quality data of helminth genomes provided over the past two decades has supported and accelerated large-scale ‘omics studies and, consequently, the achievement of a more in-depth molecular characterization of a number of pathogens. This has also involved Strongyloides spp. and since their genome was made available transcriptomics has been rather frequently applied to investigate gene expression regulation across their life cycle. Strongyloides proteomics characterization has instead been somehow neglected, with only a few reports performing high-throughput or targeted analyses associated with protein identification by tandem mass spectrometry. Such investigations are however necessary in order to discern important aspects associated with human strongyloidiasis, including understanding parasite biology and the mechanisms of host–parasite interaction, but also to identify novel diagnostic and therapeutic targets. In this review article, we will give an overview of the published proteomics studies investigating strongyloidiasis at different levels, spanning from the characterization of the somatic proteome and excretory/secretory products of different parasite stages to the investigation of potentially immunogenic proteins. Moreover, in the effort to try to start filling the current gap in host-proteomics, we will also present the first serum proteomics analysis in patients suffering from human strongyloidiasis. This article is part of the Theo Murphy meeting issue ‘ Strongyloides : omics to worm-free populations’.

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Secreted filarial nematode galectins modulate host immune cells

Cited by 9 publications

References 91 publications

Identification of biomarker candidates for filarial parasite infections by analysis of extracellular vesicles

Identification of biomarker candidates for filarial parasite infections by analysis of extracellular vesicles

The Immune Response to Nematode Infection

Progresses and challenges in Strongyloides spp. proteomics

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