Select human milk oligosaccharides directly modulate peripheral blood mononuclear cells isolated from 10-d-old pigs
Sarah S Comstock1, Mei Wang1, Shelly N Hester2
1Department of Food Science and Human Nutrition, University of Illinois, 339 Bevier Hall, 905 S. Goodwin Avenue Urbana, IL 61801, USA.
Insights
Human milk oligosaccharides (HMO) directly impact neonatal immune cells, influencing T-cell responses and cytokine production. Formula-fed infants show different immune cell responses compared to sow-reared infants, highlighting the importance of HMO in early immune development.
Area of Science:
- Immunology
- Neonatal Nutrition
- Glycobiology
Background:
- Human milk oligosaccharides (HMO) are crucial for infant immune system development, but infant formulas lack their complexity.
- Limited research exists on the direct effects of HMO on neonatal immune cells.
- Understanding HMO's role is vital for optimizing infant nutrition and health outcomes.
Purpose of the Study:
- To investigate the direct ex vivo effects of various human milk oligosaccharides (HMO) on neonatal immune cells.
- To analyze how HMO, individually or in mixtures, influences T-cell phenotype, cytokine production, and proliferation.
- To compare immune cell responses between sow-reared and formula-fed neonatal pigs.
Main Methods:
- Peripheral blood mononuclear cells (PBMC) from neonatal pigs were isolated and stimulated with single HMO, HMO mixtures, or complex iHMO.
- T-cell phenotype, cytokine (IL-10) production, and cell proliferation ([³H]thymidine incorporation) were measured.
- Immune cell responses were assessed both with direct HMO stimulation and co-stimulation with mitogens (PHA, LPS).
Main Results:
- HMO directly modulated PBMC functions, with iHMO increasing IL-10 production and fucosylated HMO reducing proliferation.
- Co-stimulation with HMO altered responses to PHA and LPS, affecting T-cell populations (CD4+CD8+) and proliferation.
- Significant differences in baseline PBMC responses were observed between sow-reared and formula-fed pigs, indicating a diet-dependent effect.
Conclusions:
- Human milk oligosaccharides (HMO) exert direct effects on neonatal peripheral blood mononuclear cells (PBMC), influencing their function and phenotype.
- The composition of HMO, including fucosylated and sialylated types, differentially impacts immune cell responses.
- Neonatal diet significantly influences ex vivo immune cell function, underscoring the importance of HMO in infant formula development.
Abstract:
Infant formulas lack the complex mixture of oligosaccharides found in human milk. These human milk oligosaccharides (HMO) may be pivotal to the development of the neonatal immune system. Few comprehensive analyses of the effects of HMO on immune cells from neonates have been undertaken. Herein, the direct effects of HMO on immune cells were analysed ex vivo. Peripheral blood mononuclear cells (PBMC) isolated from 10-d-old sow-reared (SR) or colostrum-deprived formula-fed (FF) pigs were stimulated for 72 h with single HMO, mixtures of single HMO or a complex mixture of HMO isolated from human milk (iHMO). T-cell phenotype, cytokine production and proliferation were measured by flow cytometry, immunoassay and [³H]thymidine incorporation, respectively. Stimulation with HMO had direct effects on PBMC. For instance, cells stimulated with iHMO produced more IL-10 than unstimulated cells, and cells stimulated with fucosylated HMO tended to proliferate less than unstimulated cells. Additionally, co-stimulation with HMO mixtures or single HMO altered PBMC responses to phytohaemagglutinin (PHA) or lipopolysaccharide (LPS) stimulation. Compared with PBMC stimulated with PHA alone, cells co-stimulated with iHMO and PHA proliferated more and had fewer detectable CD4⁺CD8⁺ T cells. Compared with PBMC stimulated by LPS alone, cells co-stimulated with a mixture of sialylated HMO and LPS proliferated more and tended to have fewer detectable CD4⁺ T cells. Differences in the baseline responses of PBMC isolated from the SR or FF pigs were observed. In summary, HMO directly affected PBMC populations and functions. Additionally, ex vivo measurements of PBMC phenotype, cytokine production and proliferation were influenced by the neonate's diet.
