Products of Fourth-Stage Larvae of Oesophagostomum dentatum Induce Proliferation in Naive Porcine Mononuclear Cells

Abstract

Infection of pigs with Oesophagostomum dentatum is a major cause of economic losses in pig productions. Whether infection with this nematode results in a protective immunity is still in debate and information about immune-modulating properties of O. dentatum are lacking. The present study investigated the question whether products of O. dentatum larvae modulate the proliferative response of porcine blood mononuclear cells (poMNC) in vitro. The poMNC of naïve and O. dentatum-infected pigs were cultured for 72 h in the presence of products (total homogenates and culture supernates) derived from third- (L3) and fourth-stage larvae (L4) of O. dentatum. Numbers of vital cells and blast-transformed cells were determined flow cytometrically. No larvae product induced an accelerated death of poMNC in vitro. In contrast, products of L4 (but not L3) significantly increased the numbers of vital poMNC in vitro (up to 187%). In addition, L4 products (homogenates and supernates, 0.1-10 microg/ml) but not those of L3 induced significant blastogenesis of poMNC. This was seen with poMNC from naïve and from O. dentatum-infected animals. In spite of these effects, the larvae products were not able to modulate the mitogen-induced (Concanavalin A) poMNC proliferation of naïve and infected animals. In summary, larvae of O. dentatum contain and secrete products with potential immunomodulatory capacity for porcine peripheral blood mononuclear cells. The differential effects of L3 and indicate that the parasite alters its set immunomodulatory substances during its development. This has to be considered in further studies and may help to identify the mediators involved.

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“…In addition, somatic extracts of and supernatants from in vitro maintenance cultures of Oe. dentatum L4s have been shown to induce the proliferation of porcine mononuclear cells in vitro (310), which supports the hypothesis that L4-specific proteases play an active role in the modulation of the host's immune response (302)(303)(304). The results from a recent study (206) showed also that a high proportion (27-32%) of transcripts encoding protein kinases and phosphatases were common among all developmental stages of Oe.…”

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“…Indeed, unresponsiveness of antigen‐specific T cells is described during helminth infections . On the other hand, when PBMC of lungworm infected cattle were stimulated with whole worm homogenate, an increased proliferation has been shown and studies using porcine and ovine PBMC demonstrated a clear and significant proliferative response towards helminthic infections . However, mentioned studies used proteins derived from parasite homogenates or secretory products of larvae, and thus containing a mixture of protein and nonprotein components in contrast to a single recombinant protein.…”

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“…Indeed, O. dentatum L4s are known to evoke immunological reactions that result in the encapsulation of the larvae in nodules with aggregations of neutrophils and eosinophils (58,71). In addition, somatic extracts of and supernatants from in vitro maintenance cultures of O. dentatum L4s have been shown to induce the proliferation of porcine mononuclear cells in vitro (72). These observations suggest an active role for L4-specific proteases in the modulation of the host’s immune response, which (as proposed for other biological systems) could consist of: (i) the direct digestion of antibodies (68); (ii) cleavage of cell-surface receptors for cytokines (73) and/or (iii) direct lysis of immune cells (74).…”