bioRxiv Science⌕ Search

bioRxiv · 10.1101/2022.07.18.500308

Changes in biomarkers of metabolic stress during late gestation of dairy cows associated with colostrum volume and immunoglobulins content

Abstract

The objective of this observational study was to compare the metabolic status of dairy cows during the last 6 wk of gestation based on colostrum volume and Ig content. For this, healthy Holstein cows were randomly selected from 3 commercial herds in Michigan. In each farm, four cohorts of 21 cows (one per season), stratified by parity, were enrolled (n=228). Cows were blood sampled weekly during the last 6 wk of gestation, and biomarkers related to nutrient utilization, oxidant status, and inflammation were quantified in serum. Cows were milked within 6 h of calving and the volume of colostrum produced was recorded and an aliquot collected. Concentration of IgG, IgA, and IgM were measured by radial immunodiffusion. Cows were grouped into high colostrum producer (HCP) or low (LCP), high IgG (HIG) or low (LIG), high IgA (HIA) or low (LIA), and high IgM (HIM) or low (LIM). For volume category, we arbitrarily defined 6 L of colostrum (4 L for first and 2 L for second feeding of calves) as the cut-off point, whereas for IgG we used the industry standard of [&ge;] 50g/L. To create groups of low and high IgM or IgA, we used the median of these Ig as the cutoff point. Colostrum volume was lowest in winter, but no differences were observed among parity groups. Conversely, colostrum IgG concentration was highest in fall and winter, but colostrum IgM was lowest at these seasons. However, colostrum Ig content only showed a negative weak correlation with volume (Spearman rho < -0.28). Compared to LCP, HCP cows had higher concentrations of antioxidant potential, BHB and lower cholesterol and oxidant status index. HIG cows showed higher concentrations of glucose compared to LIG. HIA cows had higher concentrations of cholesterol, reactive oxygen and nitrogen species, oxidant status index, and total protein, while BHB, and glucose were lower compared with LIA. Biomarkers of metabolic stress were not significantly different between HIM and LIM. Nevertheless, the differences observed did not result in differences in inflammatory status between animals in any of the colostrum variable categories analyzed, suggesting that physiological homeostasis was not disrupted during late gestation in association with the colostrum variables studied. Overall, the great variability observed in colostrum variables suggests that colostrogenesis is a complex and multifactorial process. However, our results suggest that greater availability of antioxidants during late gestation could support the production of higher volumes of colostrum, which needs to be explored in future trials. INTERPRETIVE SUMMARYChanges in biomarkers of metabolic stress during late gestation of dairy cows associated with colostrum volume and immunoglobulins content. By Rossi et al., page XXXX. We investigated associations between metabolic stress during the last 6 wk of gestation and the volume and immunoglobulin content of the colostrum produced. We observed that cows producing more than 6 L of colostrum exhibited increased metabolic activity during late gestation. Also, a greater blood antioxidant activity throughout late gestation was observed in cows with higher yields of colostrum, suggesting that greater availability of antioxidants might support the production of higher volumes of colostrum. Therefore, further studies should evaluate whether supplementation with additional antioxidants supplement during late gestation can improve colostrum yield.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Rossi, R. M., Cullens, F., Bacigalupo Sanguesa, P., Sordillo, L., Abuelo, A.. 2022-07-19. Changes in biomarkers of metabolic stress during late gestation of dairy cows associated with colostrum volume and immunoglobulins content. https://doi.org/10.1101/2022.07.18.500308

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

HIV-1 prime-boost vaccination shapes distinct clonal trajectories and memory precursor states of Env- and Gag-specific T cells

Despite decades of HIV-1 vaccine development, the clonal and cellular determinants of durable vaccine-induced T cell memory remain incompletely understood. Here, we combined antigen-specific T cell receptor (TCR) identification, longitudinal TCR sequencing, and single-cell multi-omics to characterize Env- and Gag-specific memory precursor T cells elicited by the HIV Vaccine Trials Network (HVTN) 505 DNA prime-recombinant adenovirus serotype 5 (rAd5) boost (DNA/rAd5) vaccine regimen. We developed a generalizable high-throughput approach to identify HIV-1 Env- and Gag-specific TCRs and found distinct patterns of clonal expansion, persistence, and contribution to memory between Env- and Gag-specific CD8 T cell responses. The DNA prime and rAd5 boost differentially shaped these repertoires, with rAd5-induced clones contributing proportionally more to the Gag-specific than to the Env-specific memory precursor compartment. Single-cell immune profiling further revealed distinct memory precursor states, with Env-specific responses enriched for GZMBPRF1 cytotoxic effector-memory (EM) CD8 T cells and Gag-specific responses containing a larger cycling/proliferative population. Together, these findings demonstrate that heterologous DNA/rAd5 vaccination generates antigen-specific CD8 T cell memory with distinct clonal trajectories and cellular programs, providing new insights into how vaccine platform and antigen-specificity shape the durability and functional properties of HIV-1 specific cellular immunity.

immunology↗

MicroRNA-146a Deficiency Protects NOD Mice from Autoimmune Diabetes by Enhancing c-Rel-Dependent Regulatory T Cell Function

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by T-cell mediated destruction of pancreatic islet {beta}-cells with genetic, environmental, and molecular triggers involved in disease pathogenesis. Patients with T1D have elevated serum levels of microRNA146a (miR146a). Polymorphisms in the miR146a gene that result in reduced expression of miR146a are associated with protection from T1D. We studied physiological regulators of miR146a expression and found that both hyperglycemia and elevated O-GlcNAcylation increased miR146a expression in T cells. Peripheral blood mononuclear cells (PBMCs) from T1D patients showed increased miR146a and O-GlcNAc transferase (OGT) expression, suggesting increased O-GlcNAcylation may promote miR146a expression in T1D patients. To determine the genetic and developmental role of miR146a in T1D, we generated miR146a-knockout (KO) non-obese diabetic (NOD) mice and found that absence of miR146a significantly protected NOD mice from spontaneous autoimmune diabetes. While we found no impact of miR146a knockout on general hematopoietic parameters and immune cell populations, remarkably, immune cell infiltration into the pancreas was significantly attenuated. Protection from autoimmune diabetes in miR146a-KO NOD mice was associated with increased regulatory T (Treg) cells in the spleen and pancreatic lymph node. Mechanistically, absence of miR146a increased NF-{kappa}B c-Rel expression in Treg cells and enhanced c-Rel binding at the Forkhead box protein P3 (FOXP3) promoter, which positively regulated Treg cell development and suppressor function, offering protection from T1D in miR146a-KO NOD mice. Our findings reveal miR146a as a key regulator of Treg cell-mediated immune tolerance through controlling NF-{kappa}B c-Rel-dependent FOXP3 expression and suggest targeting miR146a as a potential strategy to restore peripheral tolerance in T1D.

immunology↗

A loopless subdomain of transferrin binding protein B can elicit a broadly cross-reactive humoral immune response targeting variants from both encapsulated and non-typeable Haemophilus influenzae

Haemophilus influenzae is a Gram-negative bacterium that causes pneumonia, otitis media, and invasive infections such as meningitis and bacteremia. A vaccine that confers protection against disease caused by H. influenzae serotype b is currently available and is highly effective, but infections caused by non-b serotypes and non-typeable strains are still prevalent and increasing, suggesting a need for a broadly cross-protective vaccine that will protect against infection by all H. influenzae strains. To address the need for broad cross-protection, this study focused on the surface lipoprotein component of the bipartite bacterial transferrin receptor, transferrin binding protein B (TbpB), which is universally present H. influenzae, irrespective of encapsulation status, and is essential for bacterial colonization and pathogenesis. To prevent vaccine escape, we assessed the sequence and structural diversity among TbpB variants derived from local and international H. influenzae isolates and observed that these sequences cluster independently of encapsulation status, suggesting that conferring protection against all H. influenzae strains regardless of capsule type or presence of a capsule using a TbpB-based vaccine is feasible. In addition, our diversity analysis also revealed that the C-terminal lobe (C-lobe) of TbpB contains several large, highly variable loops. After immunizing mice with a trivalent vaccine consisting of a representative set of TbpB variants, we found that the resulting antiserum demonstrated modest cross-reactivity against heterologous TbpB variants. However, immunizing with a loopless C-lobe (LCL) that lacks the large, highly variable loops we had identified elicited broad cross-reactivity against a panel of intact TbpB variants. This suggests that while the intact TbpB may only generate a moderately cross-reactive antibody response, a vaccine consisting of a single LCL may be able to elicit a sufficiently cross-reactive humoral response against diverse TbpB variants, and in turn, confer broad cross-protection targeting both encapsulated and non-typeable H. influenzae.

immunology↗