Mechanisms of immunity to Haemonchus contortus infection in sheep

Abstract

In two separate experiments, sheep were immunized by nine to 12 weekly immunizing infections with 4000 Haemonchus contortus third stage larva (L3), drenched with anthelminthics and maintained free of H. contortus infection for a further 12 weeks. The anamnestic cellular immune responses in both the abomasal lymph node (ALN) and mucosa of the immunized sheep were examined 3 and 5 days post challenge with 50 000 H. contortus L3. Sheep in the two experiments clearly segregated out in two distinct groups, one in which challenge larvae were obviously present in the tissues of all 12 sheep at 3 and 5 days post challenge while no challenge larvae were detected in tissues of seven of the eight sheep in the other group. In sheep in which no tissue larvae were detected, very few changes were noted in either the ALN or mucosa. In contrast, dramatic changes were observed in the cellular profiles of the ALN and mucosa after challenge infection in sheep in which larvae were observed in the abomasal tissues. In the ALN, these changes were characterized by an increase in the relative percentage of gammadelta-TCR+ T cells and B cells and an increase in the proportion of CD4+ T cells coexpressing the activation markers MHC class II and CD25. In the abomasal mucosa, an increase in the number of infiltrating CD4+ and gammadelta-TCR+ T cells and B cells was observed by 3 days postinfection and these levels were further increased at 5 days postinfection. This infiltration of the abomasal mucosa by lymphocytes was accompanied by a dramatic increase in the number of infiltrating eosinophils, which were often in intimate association with the surface of H. contortus larvae. None of these changes occurred in the mucosa of the sheep that showed no sign of challenge larvae in the tissues; however, a transient increase in gammadelta T cells in the ALN and a drop in intraepithelial globule leucocytes were uniquely observed in these sheep at 5 days post challenge. These results suggest that two different types of immune responses can be generated after challenge infection of immunized sheep, one where tissue larvae are excluded from their tissue niche as observed previously and which is associated with changes in globular leucocyte population but no mobilization of the local immune system. In contrast, when challenge larvae reach their tissue niche, dramatic changes in the local immune system occur, including a pronounced infiltration of eosinophils. These two immune mechanisms may be associated with the rapid and delayed rejection of parasite infections in immune sheep.

Haemonchus contortus(Nematoda: Trichostrongylidae) infection in lambs elicits an unequivocal Th2 immune response

“…Repetitive or continuous infections are usually used to study the host immune response and to mimic natural infections as well as possible [1,5,7]. Nevertheless, single H. contortus infections were necessary in our experiment which was mainly designed to measure host immune response effects on worm development.…”

Quantitative trait loci for internal nematode resistance in sheep: a review

“…It is unclear if the genes that control key processes and mechanisms preventing the establishment of worms in primary infections of sheep with internal nematodes are different to those involved in subsequent infections. When parasite larvae reach their tissue niche in a naïve organism an immune response is triggered resulting in an increased recruitment of lymphocytes, eosinophils, T and B cells, with a concomitant delay in worm expulsion [3]. In comparison, in sheep that have been previously exposed to internal nematodes the larvae do not reach the tissue because an immediate immune response leading to expulsion is triggered with very little change to the cell populations [3].…”

“…When parasite larvae reach their tissue niche in a naïve organism an immune response is triggered resulting in an increased recruitment of lymphocytes, eosinophils, T and B cells, with a concomitant delay in worm expulsion [3]. In comparison, in sheep that have been previously exposed to internal nematodes the larvae do not reach the tissue because an immediate immune response leading to expulsion is triggered with very little change to the cell populations [3]. Therefore it appears that different pathways are involved that may underlie the control of different genes.…”

Haemonchus Contortus and Ovine Host: A Retrospective Review.

“…Resistant breeds include St. Croix [118], Florida Native [119; 120], and Gulf Coast Native [8]. Resistance in these breeds is defined as diminished establishment of larvae and their subsequent development into adult stages [121]. Nutritional status is a key component of the host immune response and the host"s subsequent ability to mount an effective defense against GIN infection [122].…”