Differences in TLR2 pattern recognition receptor expression on blood mononuclear cells with and without ligand stimulation among dairy cattle classified by estimated breeding value (EBV) of adaptive immune response

Wagter-Lesperance, Lauraine
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University of Guelph

This thesis investigated bovine toll-like receptor 2 (TLR2), an innate pattern recognition receptor (PRR), on bovine blood mononuclear cells (BMC). BMC were evaluated from dairy cattle classified into immune response (IR) groups based on their estimated breeding values (EBV) for antibody-mediated (AMIR) and cell-mediated (CMIR) IR. The first study investigated ex-vivo TLR2 expression by IR group for AMIR and CMIR traits separately. Cattle with High (H)-AMIR had a higher percentage of cells expressing TLR2 in contrast to Average (A)-AMIR and Low (L)-AMIR groups. The second study investigated TLR2 expression ex-vivo among cattle classified into 5 IR groups based on AMIR and CMIR traits combined. For both ex-vivo studies, CD14+ monocytes had the highest percentage of cells expressing TLR2 among BMC. Cows classified in the H-AMIR/H-CMIR group had the highest TLR2 median fluorescence intensity (MFI) of all IR groups and was significantly higher compared to A-AMIR/A-CMIR cows. The third study evaluated in-vitro TLR2 expression on BMC and subsets following culture with TLR2 ligands.  After 18h of culture, the percentage of cells expressing TLR2 increased among all BMC and was highest for BAQ155A+ B cells compared to other subsets. Variation in TLR2 MFI expression induced by PAM3CSK4 and Man-LAM could be explained by pregnancy or parity fixed effects or their interaction. The fourth study evaluated in-vitro TLR2 expression and cytokine production in the context of IR group. H-AMIR/H-CMIR cows had significantly higher MFI for TLR2 expression compared to H-AMIR/L-CMIR cows following culture with PAM3CSK4 or LTA. For the CD14+ cell subset, MFI was highest for the H-AMIR/H-CMIR group compared to all other IR groups following culture with PAM3CSK4. The pattern of TLR2 MFI expression for CD14+ monocytes was different for Man-LAM in that both the L-AMIR/L-CMIR and H-AMIR/H-CMIR groups had significantly higher expression compared to other IR groups. IL-1ß was negatively associated with TLR2 expression in that the highest IL-1ß was observed with A-AMIR/A-CMIR cows and was lowest for H-AMIR/H-CMIR and L-AMIR/L-CMIR cows. The higher expression of TLR2 on BMC and associated cytokine expression among cattle that rank high for both AMIR and CMIR may contribute to enhanced adaptive IR and disease resistance.

TLR2, dairy cattle, adaptive immune response, innate host defence, TLR2 ligands, bovine toll-like receptor 2, High Immune Response (HIR), HIR technology, antibody-mediated immune response (AMIR), cell-mediated immune response (CMIR), blood mononuclear cells (BMC)