Identifying the Contributions of Interferon Responses to Disease and Pregnancy in Cattle

Abstract

Two significant challenges the cattle industry is facing are respiratory disease and infertility. The type I interferon (IFN) pathway plays a pivotal role in both disease and pregnancy. The type I IFN pathway is interrupted by viral infection which reduces production of interferon stimulated genes (ISG). Interferon-tau (IFNT) is the pregnancy recognition signal in ruminants, which acts through the type I IFN pathway to activate ISG. Thus, understanding IFN and immune function could improve production efficiency. Studies described herein evaluate type I IFN and immune responses to bovine respiratory disease and pregnancy recognition in cattle.The first experiment evaluated activation of the type I IFN pathway after infecting calves with bovine viral diarrhea virus type 1b (BVDV1b) and Mannheimia haemolytica (MH). Steady-state mRNA levels of MX1, ISG15, and RTP4 were determined in peripheral blood leukocytes prior to BVDV1b exposure (d -4), prior to MH challenge (0 h), 12 h and 24 h after MH challenge. A significant time effect (P < 0.05) for all ISG was detected. At 0 h, ISG15 levels increased 44-fold and remained elevated over 60-fold for 12 h and 24 h (P < 0.01). Likewise, RTP4 and MX1 increased at 12 h (P < 0.05) after BVDV challenge. Data suggests that the type I IFN pathway remains active after challenge with BVDV1b and MH.The second experiment evaluated pregnancy rates after intrauterine, autologous transfer of IFNT-primed immune cells. Peripheral blood mononuclear cells were cultured overnight with 500 U/mL of IFNT, followed by autologous intrauterine transfer (IMMUNE; n = 97) on d 4 after estrus; controls received intrauterine infusion of saline (CONT; n = 82). On d 7, serum samples were collected for hormone analysis and embryos were transferred to all animals. Progesterone concentrations were similar for IMMUNE (4.1 � 0.33 ng/mL) and CONT (3.7 � 0.33 ng/mL) and were not different between pregnant and open cows (P > 0.2). Pregnancy rate for IMMUNE was 77% (75/97) compared with 57% (47/82) for CONT (P < 0.01). Results indicate that progesterone concentrations did not differ between groups and transfer of autologous IFNT-primed PBMC improved pregnancy rates after embryo transfer.