A proteomic approach to identify proteins from Trichuris trichiura extract with immunomodulatory effects

Abstract

Infections with Trichuris trichiura and other trichurid nematodes have been reported to display protective effects against atopy, allergic and autoimmune diseases. The aims of the present study were to investigate the immunomodulatory properties of T. trichiura adult worm extract (TtE) and its fractions (TtEFs) on the production of cytokines by peripheral blood mononuclear cells and to identify their proteinaceous components. Fourteen TtEFs were obtained by ion exchange chromatography and tested for effects on cytokine production by peripheral blood mononuclear cells. The molecular constituents of the six most active fractions were evaluated using nano-LC/mass spectrometry. The homology between T. trichiura and the related nematode Trichinella spiralis was used to identify 12 proteins in TtEFs. Among those identified, fructose biphosphate aldolase, a homologue of macrophage migration inhibitory factor and heat-shock protein 70 may contribute to the immunomodulatory effects of TtEFs. The identification of such proteins could lead to the development of novel drugs for the therapy of allergic and other inflammatory diseases.

Characterisation of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication

“…Despite this progress, and the tractability of the T. muris model, very few proteomic studies have been conducted, and only a handful of reports have described proteins secreted by Trichuris spp. [9, 10, 11, 12, 13, 14]. Drake et al characterised a pore-forming protein that T. muris [14] and T. trichiura [13] use to drill holes in the host cell membrane.…”

Proteomic Analysis Of Trichuris Trichiura Egg Extract Reveals Potential Immunomodulators And Diagnostic Targets

“…The most abundant transcripts found in this extensive study, included proteins we have also identi ed in the EE proteome such as two WAP domain containing SLP-like proteins, protease inhibitors such as Cystatin-domain containing protein and nematode cuticle collagen N-terminal domain containing proteins and Chitin binding domain containing proteins such as CBM14 domain containing proteins. Furthermore, with more or less representation, but of particular interest within the context of the present work, we have found trichuris egg proteins with known immunomodulatory properties such as Macrophage migration inhibitory factor homolog (MIF), previously identi ed in T. trichiura adult [14], and 14-3-3 protein which has also been identi ed in several developmental stages of other nematodes, Trichinella britovi [31] and Trichinella spiralis [32] and trematodes, Schistosoma japonicum [33]. Both proteins are considered as enhancers of humoral and cellular immune responses [34].…”

“…While T. trichiura somatic and excretion/secretion products from the adults have been studied in depth and have been shown to elicit protective immune responses [13][14][15][16], other life-cycle stages of the parasite, such as the eggs, have not been fully investigated. Only a few reports indicate that they may be modulators of the immune system, and recognize them as potential sources of diagnostic antigens [17,18].…”

“…Interestingly, the administration of embryonated eggs from the animal species Trichuris suis or Trichuris muris to humans has been described as potential therapeutic agents for immune-related pathologies such as chronic intestinal in ammatory diseases, emphasizing their capacity to downregulate aberrant intestinal in ammation [6,[19][20][21][22]. Their immunomodulatory capacity continues to be investigated with some studies trying to identify the molecules responsible for those effects [14,[22][23][24][25].…”

Perusal of parasitic nematode ‘omics in the post-genomic era

“…Curiously, 2/3 of miRNAs are most abundant in larval stages rather than in adults, with a significant decrease in the L3-L4 transition, suggestive of developmental regulation [15]. Consistent with evidence that trichurid nematodes may protect against allergic reactions, atopy, and autoimmune conditions [17], proteins such as fructose bisphosphate aldolase and heat shock protein 70 have been identified as potential immunomodulatory agents [18, 19]. Trichuris spp.…”