Submitted to: Infection and Immunity
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/30/2005
Publication Date: 9/15/2005
Citation: Claerebour, E., Vercauteren, I., Geldhof, P., Olbrechts, A., Zarlenga, D.S., Goddeeris, B.M., Vercruysse, J. 2005. Cytokine responses in the abomasum of immunized and non-immunized calves after ostertagia ostertagi infection. Infection and Immunity. 27:325-331. 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 protective antigen fractions from each of the important stages of the parasite for their ability to generate immune and protective responses in the host resulting from a trickle infection. In addition, these same antigens were evaluated in vitro on a more defined subset of cells to better understand the parasites ability to regulate host immune responses and thereby promote infection. Results indicated that under low infection densities, an immune response characteristic of nematode infections in model systems was observed; however, in vitro, antigen from the 4th larvae induced a response that was contradictory to model systems. 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: The objective of this study was to evaluate abomasal cytokine responses in helminth naive calves and calves vaccinated with protective antigen fractions from Ostertagia ostertagi after an experimental challenge infection with infective third stage (L3) larvae. Abomasal lymph nodes and/or abomasal mucosa were collected and messenger RNA for the Th1 cytokines (IFN g, IL 2, IL 12 p40 subunit), the Th2 cytokines (IL 4, IL 5, IL 6, IL 10, IL 13, IL 15) and the Th3/Tr cytokine TGF b was quantified by real time RT PCR. Vaccination had no effect on cytokine profiles in either the abomasal lymph nodes or the abomasal mucosa. However, following infection all calves showed a significant decrease in the Th1 cytokines, IFN g and IL 12 p40, and a significant increase in the Th2 cytokines, IL 4, IL 5, IL 10 and IL 13 in the lymph nodes, compared to non infected calves. In contrast, a Th2 pattern was not observed in the mucosa of the infected calves, which exhibited an increase in IFN g and IL 5 mRNA, only. No significant association was observed in the abomasal mucosa between any examined cytokine mRNA level and immune effector responses such as parasite specific antibodies or the number of mucosal mast cells or eosinophils. Abomasal lymph node lymphocytes from 3 experimentally infected, non immunized calves were stimulated in vitro with Ostertagia L3, L4 or adult antigen extract. Antigen derived from L3 or adult parasite induced IL 4, IL 10 and IL 13 transcriptional changes, whereas stimulation with extract from all parasitic stages gave rise to IL 6 and IFN g mRNA as well. These data suggest that infection with O. ostertagi stimulates a predominantly Th2 cytokine response in the abomasal lymph nodes, although IFN g was also upregulated after in vitro stimulation. No correlation between the Th2 response and protection induced by vaccination could be demonstrated.