Activation of Basophils by Gastrointestinal Nematode Parasites

Abstract

Gastrointestinal nematodes (GINs) pose a major risk to the farming of small ruminants worldwide. Typically GIN infections are controlled by anthelmintics, however the success of such programs are threatened by widespread emergence of anthelmintic resistance in parasite populations. Vaccine technology based on humoral antibody protection has been developed against 'Haemonchus contortus', however the mechanism of protection is ineffective for parasites such as 'Trichostrongylus colubriformis' that do not access the blood. The danger hypothesis suggests a link between tissue damage and the initiation of the correct immune response, theorising that an antigen must be presented in context of a danger signal. The host danger signals may provide the context of the immune response whilst the antigens provide the targets for the immune system. In the current study the activation state of basophils cultured with epithelial cells and 'T. colubriformis' larvae in the presence of mucin or Ivermectin was determined using a basophil specific activation marker (CD203). The expression and intensity of CD164, CD107a and CD13 in gated CD203+ cell populations was then determined. CD164 was upregulated only by contact with epithelial cells and CD107a showed no significant change. In the presence of only epithelial cells and 'T. colubriformis' but lacking mechanisms to limit worm motility, the mean fluorescence intensity of CD13 was significantly inhibited. These results suggest that 'T. colubriformis' movement may cause inhibition of basophil activation, whilst limiting worm motility allows an amplified immune response. Future studies will establish an immune cell-epithelial cell-parasite culture system allowing examination of cell-mediated immune responses at the site of infection to formulate a mucosal delivery vaccine.