Modulation of weanling pig cellular immunity in response to diet supplementation with 25-hydroxyvitamin D(3).

There is still significant debate over the effects that vitamin D3 has on the immune system, as both pro-inflammatory and anti-inflammatory cellular responses have been described. The objective of this study was to use a weanling pig model of nutritional supplementation to provide a broad functional look at the immune cellular changes that occur as a result of vitamin D3 nutritional supplementation. We identified a significant impact on cellular immune parameters, particularly in pigs supplemented with a commercial hydroxylated version of vitamin D3, 25-hydroxyvitamin D3 [25(OH)D3; Hy·D]. We found that significant increases in leukocyte cell numbers reflected parallel increases in serum 25(OH)D3. Multi-site, multi-parametric analysis of functional traits also showed positive modulation of leukocyte survival and phagocytic capacity across blood and bronchoalveolar compartments, highlighting the potential impact on systemic and mucosal antimicrobial responses. In all, our work supports previous observations regarding the positive immunomodulatory role of vitamin D3 and points to 25(OH)D3 (Hy·D) as a superior dietary supplement for weanling pigs.

Fish and mammalian phagocytes differentially regulate pro-inflammatory and homeostatic responses in vivo.

Phagocytosis is a cellular mechanism that is important to the early induction of antimicrobial responses and the regulation of adaptive immunity. At an inflammatory site, phagocytes serve as central regulators for both pro-inflammatory and homeostatic anti-inflammatory processes. However, it remains unclear if this is a recent evolutionary development or whether the capacity to balance between these two seemingly contradictory processes is a feature already displayed in lower vertebrates. In this study, we used murine (C57BL/6) and teleost fish (C. auratus) in vitro and in vivo models to assess the evolutionary conservation of this dichotomy at a site of inflammation. At the level of the macrophage, we found that teleost fish already displayed divergent pro-inflammatory and homeostatic responses following internalization of zymosan or apoptotic bodies, respectively, and that these were consistent with those of mice. However, fish and mice displayed significant differences in vivo with regards to the level of responsiveness to zymosan and apoptotic bodies, the identity of infiltrating leukocytes, their rate of infiltration, and the kinetics and strength of resulting antimicrobial responses. Unlike macrophages, significant differences were identified between teleost and murine neutrophilic responses. We report for the first time that activated murine, but not teleost neutrophils, possess the capacity to internalize apoptotic bodies. This internalization translates into reduction of neutrophil ROS production. This may play an important part in the recently identified anti-inflammatory activity that mammalian neutrophils display during the resolution phase of inflammation. Our observations are consistent with continued honing of inflammatory control mechanisms from fish to mammals, and provide added insights into the evolutionary path that has resulted in the integrated, multilayered responses that are characteristic of higher vertebrates.