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

Yates, Devyn; Di Maggio, Lucia S.; Rosa, Bruce A.; Sprung, Robert W.; Erdmann-Gilmore, Petra; Townsend, R. Reid; Budge, Philip J.; Kamgno, Joseph; Mitreva, Makedonka; Weil, Gary J.; Fischer, Peter U.

doi:10.3389/fpara.2023.1281092

Front. Parasitol.

2023

DOI: 10.3389/fpara.2023.1281092

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

Devyn Yates,

Lucia S. Di Maggio,

Bruce A. Rosa

et al.

Abstract: 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 mi… Show more

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2024

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Cited by 3 publications

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An in-depth exploration of the multifaceted roles of EVs in the context of pathogenic single-cell microorganisms

Feix,

Tabaie,

Singh

et al. 2024

Microbiol Mol Biol Rev

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SUMMARY Extracellular vesicles (EVs) have been recognized throughout scientific communities as potential vehicles of intercellular communication in both eukaryotes and prokaryotes, thereby influencing various physiological and pathological functions of both parent and recipient cells. This review provides an in-depth exploration of the multifaceted roles of EVs in the context of bacteria and protozoan parasite EVs, shedding light on their contributions to physiological processes and disease pathogenesis. These studies highlight EVs as a conserved mechanism of cellular communication, which may lead us to important breakthroughs in our understanding of infection, mechanisms of pathogenesis, and as indicators of disease. Furthermore, EVs are involved in host–microbe interactions, offering insights into the strategies employed by bacteria and protozoan parasites to modulate host responses, evade the immune system, and establish infections.

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An in-depth exploration of the multifaceted roles of EVs in the context of pathogenic single-cell microorganisms

Feix,

Tabaie,

Singh

et al. 2024

Microbiol Mol Biol Rev

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A novel antigen biomarker for detection of high-level of Loa loa microfilaremia

Greene,

Huang,

Fischer

et al. 2024

PLoS Negl Trop Dis

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Background Loiasis is a disease caused by the nematode Loa loa. Serious adverse events sometimes occur in people with heavy L. loa microfilaremia after ivermectin treatment. In regions of Central Africa where loiasis is endemic, this significantly impedes global elimination programs for lymphatic filariasis and onchocerciasis that use mass distribution of ivermectin. Improved diagnostic tests to identify individuals at increased risk of serious adverse events could facilitate efforts to eliminate lymphatic filariasis and onchocerciasis in this region. Methods and findings We previously identified the L. loa protein Ll-Bhp-1 in loiasis patient sera. Here, we further characterize Ll-Bhp-1 and report development of an antigen capture ELISA to detect this antigen. This assay detected Ll-Bhp-1 in 74 of 116 (63.8%) loiasis patient sera. Ll-Bhp-1 levels were significantly correlated with L. loa microfilarial counts, and the sensitivity of the assay was highest for samples from people with high counts, (94% and 100% in people with ≥20,000 and ≥50,000 microfilaria per milliliter of blood, respectively). The antigen was not detected in 112 sera from people with other filarial infections, or in 34 control sera from the USA. Conclusions This Ll-Bhp-1 antigen assay is specific for loiasis, and highly sensitive for identifying people with high L. loa microfilarial counts who are at increased risk for serious adverse events after ivermectin treatment. L. loa antigen detection has the potential to facilitate loiasis mapping efforts and programs to eliminate lymphatic filariasis and onchocerciasis in Central Africa.

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Brugia malayi filarial helminth-derived extracellular vesicles suppress antigen presenting cell function and antigen-specific CD4+ T cell responses

Sanku,

Ricciardi,

Redekar

et al. 2024

Front. Immunol.

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IntroductionLive microfilariae (mf) and mf-derived extracellular vesicles (EVs) have been shown to modulate human antigen presenting cell (APC) function, most notably by suppressing the induction of IL-12 (and other pro-inflammatory cytokines) following activation with LPS and interferon-y. MethodsTo explore further how EVs alter human APC function, we studied the effect of mf and EVs on human elutriated monocyte-derived dendritic cells (DC) following exposure to Mf, mf-derived excretory/secretory (E/S) products, E/S depleted of EVs through ultracentrifugation and purified EVs. After demonstrating that the measurable responses induced by live mf could be recapitulated by EVs and EV-containing E/S, we next performed RNAseq analysis of human DC following exposure to live mf, EVs, E/S, or EV-depleted E/S. ResultsIn our analyses of the data for the DC, using a false discovery rate (FDR)<0.05, EV-exposed DC had induced the expression of 212 differentially expressed genes (DEGs) when compared to unexposed DC and 157 when compared to E/S-depleted EVs. These genes were enriched in GO biological processes associated with neutrophil degranulation and 15 DEGs associated with KEGG Lysosome pathways. IPA analysis point to immune dysregulation. We next aimed to understand the intracellular processes altered by EVs and the effect these have on effector T cells. When SARS CoV-2 Membrane-specific CD4+ TCLs were assessed following EV conditioning of autologous DC and activation with the SARS CoV-2-Membrane peptide pool, we found conditioning reduced the frequency of SARS CoV-2 Membrane-specific CD3+ CD4+ CD154+ cells (p=.015). Similarly, EV-conditioning of SARS CoV-2 Membrane-specific CD3+ CD4+ cells induced fewer cell capable of producing IFN-γ (p=.045). DiscussionTaken together, our data suggest a modulatory role of EVs on APC function that likely leads to defects in T cell effector function.

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

Cited by 3 publications

References 62 publications

An in-depth exploration of the multifaceted roles of EVs in the context of pathogenic single-cell microorganisms

An in-depth exploration of the multifaceted roles of EVs in the context of pathogenic single-cell microorganisms

A novel antigen biomarker for detection of high-level of Loa loa microfilaremia

Brugia malayi filarial helminth-derived extracellular vesicles suppress antigen presenting cell function and antigen-specific CD4+ T cell responses

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