Maternal body condition influences neonatal calf whole-blood innate immune molecular responses to ex vivo lipopolysaccharide challenge

Abstract

Managing body condition in dairy cows during the close-up period could alter the availability of nutrients to the fetus during the final growth stages in utero. We investigated how maternal body condition score (BCS) in late pregnancy affected calf whole-blood mRNA abundance and IL-1β concentrations after ex vivo lipopolysaccharide (LPS) challenge. Thirty-eight multiparous Holstein cows and their calves from a larger cohort were retrospectively grouped by prepartal BCS as normal BCS (≤3.25; n = 22; NormBCS) and high BCS (≥3.75; n = 16; HighBCS). Calf blood samples collected at birth (before receiving colostrum, d 0) and at ages 21 and 42 d (at weaning) were used for ex vivo whole-blood challenge with 3 µg/mL of LPS before mRNA isolation. Target genes evaluated by real-time quantitative PCR were associated with immune response, antioxidant function, and 1-carbon metabolism. Plasma IL-1β concentrations were also measured. Responses in plasma IL-1β and mRNA abundance were compared between LPS-challenged and nonchallenged samples. Statistical analyses were performed at all time points using a MIXED model in SAS 9.4. Neither birth body weight (NormBCS = 43.8 ± 1.01 kg; HighBCS = 43.9 ± 1.2 kg) nor colostrum IgG concentration (NormBCS = 70 ± 5.4 mg/mL; HighBCS = 62 ± 6.5 mg/mL) differed between groups. At birth, whole blood from calves born to HighBCS cows had greater mRNA abundance of IL1B, NFKB1, and GSR and lower GPX1 and CBS abundance after LPS challenge. The longitudinal analysis of d 0, 21, and 42 data revealed a BCS × age effect for SOD2 and NOS2 due to lower mRNA abundance at 42 d in the HighBCS calves. Regardless of maternal BCS, mRNA abundance decreased over time for genes encoding cytokines (IL1B, IL6, IL10, TNF), cytokine receptors (IRAK1, CXCR1), toll-like receptor pathway (TLR4, NFKB1), adhesion and migration (CADM1, ICAM1, ITGAM), and antimicrobial function (MPO). Concentration of IL-1β after LPS challenge was also markedly lower at 21 d regardless of maternal BCS. Overall, results suggested that maternal BCS in late prepartum influences the calf immune system response to an inflammation challenge after birth. Although few genes among those studied were altered due to maternal BCS, the fact that genes related to oxidative stress and 1-carbon metabolism responded to LPS challenge in HighBCS calves underscores the potential role of methyl donors (e.g., methionine, choline, and folic acid) in the early-life innate immune response.