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Title: INHIBITION OF BOVINE T LYMPHOCYTE RESPONSES BY EXTRACTS OF THE STOMACH WORM OSTERTAGIA OSTERTAGI.

Author
item GOMEZ,MUNOZ, M - SPAIN
item CANALS-CABALLERO, A - SPAIN
item ALMERIA, S - SPAIN
item PASQUALI, P - ITALY
item Zarlenga, Dante
item Gasbarre, Louis

Submitted to: Veterinary Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/14/2004
Publication Date: 3/25/2004
Citation: Gomez,Munoz, M.T., Canals-Caballero, A., Almeria, S., Pasquali, P., Zarlenga, D.S., Gasbarre, L.C. 2004. Inhibition of bovine t lymphocyte responses by extracts of the stomach worm ostertagia ostertagi.. Veterinary Parasitology 125(3):199-214.

Interpretive Summary: The parasite, Ostertagia ostertagi, is among the most costly to the cattle industry in terms of economic losses, and is the most difficult among the trichostrongyles for the host to protect against. Research was initiated to evaluate proteins from each of the parasite's life cycle stages for their ability to down-regulate host immune responses and thereby promote infection. Results indicated that secreted peptides from the later part of the 4th stage induced such a response. Given that this same stage is responsible also for most of the pathology associated with the infection, this research has allowed us to begin targeting late L4 proteins as a means to attenuate or eliminate the deleterious effects of the infection which occur commensurate with establishment of the parasite in the host.

Technical Abstract: Lowered immune responses during bovine ostertagiosis have been reported in both in vivo and in vitro assay systems. In the present study we have employed three different life cycle stages of the nematode Ostertagia ostertagi to determine if products of this economically important parasite inhibit in vitro proliferation of ConA-stimulated cells from uninfected animals. We have demonstrated an inhibitory effect upon the growth of Con A-stimulated lymphocytes after addition of fourth stage larval (L4) soluble extract (L4SE) to the cultures. In contrast, extracts from the third stage larvae (L3) had little or no inhibitory activity. The suppressive products were also shown to be secreted by the late L4. The suppressive activity is reversible if the L4 products are removed from culture. There is no immediate effect on proliferating cells and the L4SE must be in culture for 24-48 hours before suppression is observable. The L4SE caused slight but not statistically significant decreases in the percentage of T cells and increases in B cell percentages in cultures when compared with cultures stimulated with Con A alone. No changes were seen in percentage of cells positive for markers for CD4, CD8, '' T cells, or monocytes/macrophages as a consequence of the addition of L4SE. In contrast, there was a strong and significant reduction in the expression of the IL2 receptors in cells cultured in the presence of the worm extract. There was no evidence of either necrosis or apoptosis resulting from the presence of L4 products in culture. The expression of messenger RNA for Interleukins 2, 4, 13, Tumor Necrosis Factor-alpha (TNF-'),and gamma-Interferon ('-IFN) was decreased when L4 SE was included in cultures of Con A stimulated cells compared to cultures stimulated with Con A only. In contrast, messenger RNA expression of Transforming Growth Factor-beta (TGF-ß) and Interleukin-10 (IL10) was increased in cells growing in the presence of L4 products. The potential role of these cytokines during ostertagiosis is discussed.