Search bioRxiv⌕ Search

bioRxiv · 10.1101/2023.07.26.550707

Understanding the Immunomodulatory Effects of Bovine Colostrum: Insights into IL-6/IL-10 Axis-Mediated Inflammatory Control

Abstract

Bovine colostrum (COL), the first milk secreted by lactating cows postpartum, is a rich source of bioactive compounds that exert significant role on the survival, growth, and immune development of neonatal calves [9,10]. This study investigated the immunomodulatory effects of COL on cytokine production in vitro using a Caco-2/THP-1 macrophage co-culture model stimulated with Phorbol 12-myristate 13-acetate (PMA). COL pretreatment significantly reduced IL-6 production induced by PMA, while increasing IL-10 production. Further investigations revealed that the IL-6 suppressive effect of colostrum was heat-sensitive and associated with components of higher molecular mass (100 kDa). Moreover, colostrum primarily influenced THP-1 macrophages rather than Caco-2 epithelial cells. The effects of colostrum on IL-6 production were associated with reduced NF-{kappa}B activation in THP-1 macrophages. In calf-FMT transplanted C57BL/6 murine model, colostrum decreased intestinal permeability, reduced immune cell infiltration, and suppressed IL-6 production during S. typhimurium infection. These results highlight the immunomodulatory activity of bovine colostrum and its potential therapeutic applications in inflammatory disorders. Further studies are needed to elucidate the underlying mechanisms and validate the findings in bovine models. Simple SummaryThis study explores the immunomodulatory properties of bovine colostrum (COL), the initial milk produced by lactating cows, on cytokine production in vitro and in a novel murine calf-FMT model. The researchers utilized a Caco-2/THP-1 macrophage co-culture model stimulated with Phorbol 12-myristate 13-acetate (PMA) to investigate the effects of COL on cytokine production. The findings indicate that COL pretreatment significantly reduced IL-6 production while enhancing IL-10 production. The IL-6 suppressive effect was heat-sensitive and associated with components of higher molecular mass (100 kDa). Colostrum demonstrated decreased intestinal permeability, reduced immune cell infiltration, and suppressed IL-6 production during S. typhimurium infection. These results highlight the immunomodulatory potential of bovine colostrum and its prospective therapeutic applications in inflammatory disorders. Further research is necessary to elucidate the underlying mechanisms and corroborate the findings in bovine models.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Grigaleviciute, R., Matusevicius, P., Planciuniene, R., Stankevicius, R., Radzeviciute-Valciuke, E., Baleviciute, A., Zinkeviciene, A., Zigmantaite, V., Kucinskas, A., Kavaliauskas, P.. 2023-07-28. Understanding the Immunomodulatory Effects of Bovine Colostrum: Insights into IL-6/IL-10 Axis-Mediated Inflammatory Control. https://doi.org/10.1101/2023.07.26.550707

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

KEEP EXPLORING

Related preprints

Nlrp6-dependent sentinel goblet cell functions dictate defensive responses during bacterial invasion of colonic crypts

The intestinal mucus layer serves as the primary physical barrier against microbial invasion, shielding the epithelium from luminal pathogens and inflammatory insults. This barrier is maintained by a heterogeneous population of goblet cells (GCs), which secrete regionally and organizationally distinct mucus layers. However, when this primary barrier is compromised, the burden of defense likely shifts to secondary mechanisms that remain incompletely defined. Therefore, we aimed to investigate the proposed role of microbe-sensing sentinel goblet cells (senGCs) as a secondary defensive mechanism that becomes critical when the primary mucus barrier fails, focusing on their capacity to mount localized secretory responses and preserve crypt sterility under challenge conditions. Using a GC specific Nlrp6 knockout model (Nlrp6{Delta}GC), we demonstrate that senGC deficiency leads to increased susceptibility to DSS induced colitis and Citrobacter rodentium infection, marked by exacerbated inflammation and enhanced crypt invasion respectively. Transcriptomic and immunolgical profiling revealed both common and sex-specific immune dysregulation, with especially female Nlrp6{Delta}GC mice exhibiting heightened mucosal pathogen burden, reduced Th17 expansion and increased CD8 T cell recruitment. The senGC-deficient mice also showed diminished baseline mucus secretion and accelerated GC loss during infection, suggesting a previously unrecognized mucus maintenance role for senGCs. Furthermore, infection induced expansion of Nlrp6 GCs in wild-type mice, enhancing MAMP-triggered mucus secretion, a response that is absent in Nlrp6{Delta}GC tissue. These findings confirm senGCs as an important regulator of epithelial protection by integrating GC-intrinsic microbial sensing with mucosal defense.

immunology↗

Exploratory positional differences in observed CDRH2 lineage-state transitions following HIV-1 germline-targeting vaccination

Background: Germline-targeting HIV-1 vaccination recruits VRC01-class B-cell precursors, but the positional patterns of observed longitudinal B-cell receptor lineage-state changes remain incompletely described. We compared CDRH2 profiles between homologous and heterologous boosting regimens using published IAVI G002 data. Methods: Participant-specific Week-8 lineages were prospectively matched to Week-24 observations. Germline-to-nongermline changes in sampled lineage-modal residues were evaluated at seven IGHV1-2*02 CDRH2 positions using participant-balanced, mean-centered profiles and exact participant-label permutation inference. Sampling-depth and sorting-probe sensitivity analyses assessed observability. A separate participant-held-out benchmark evaluated antibody-language-model representations for predicting observed Week-24 lineage detection. Results: The CDRH2 analysis included 332 lineages, 15 participants, 2,179 eligible lineage-position observations, and 241 observed state changes. The regional profile statistic was 0.027066 (exact p = 0.001709; six-region adjusted q = 0.010256), with descriptive differences at V-relative positions 51, 54, and 55. Most eligible longitudinal observations had one assessable cell per visit. In seven Group-1 participants, Week-24 dual-probe sampling recovered 181 baseline lineages with eOD-GT8 and 143 with Cg28v2, including 60 detected by both probes. In a separate cohort of 2,739 lineages from 17 participants, IgBERT and AbLang-2 representations did not improve participant-balanced average precision over a four-feature biological baseline. Conclusions: Observed CDRH2 lineage-modal-state profiles differed between regimens in this exploratory secondary analysis. Sparse sampling, potentially probe-related ascertainment, and absent linked functional validation preclude inference about mutation timing, functional improvement, or causal booster effects.

immunology↗

Multivalent mRNA tuberculosis vaccines protect against mycobacterial infection in zebrafish, mice and guinea pigs

Despite a century of BCG use, tuberculosis remains a leading cause of death from infectious diseases and more effective vaccines are urgently needed. Here we combined antigen discovery in zebrafish with mRNA vaccine technology to generate multivalent vaccine candidates, TUmRNA4, TUmRNA6 and TUmRNA9, encoding four, six, or nine Mycobacterium tuberculosis antigens, respectively. The vaccines were well tolerated, and induced robust antigen-specific cellular immune responses, including IFN{gamma} production and expansion of memory T-cell populations. In mice, TUmRNA4 and TUmRNA6 reduced pulmonary M. tuberculosis burden and lung pathology to levels comparable to BCG vaccination and TUmRNA6 enhanced BCG-mediated protection when used as a booster vaccine. In guinea pigs, TUmRNA9 reduced bacterial burden in the lungs, spleen, and lymph nodes and decreased pulmonary lesions. These findings demonstrate that protective antigens identified in zebrafish can be translated into effective multivalent mRNA vaccines and establish a framework for tuberculosis vaccine development across multiple preclinical models.

immunology↗