Extremely Low Doses of CpG Oligodeoxynucleotides From <scp> <i>Streptococcus thermophilus</i> </scp> <i>LacZ</i> Strongly Induce CXCL5 in Macrophages

Infectious diseases pose significant challenges to livestock production, compromising animal health and reducing economic productivity. To address these challenges, CpG-oligodeoxynucleotides (CpG-ODNs) have emerged as promising immunomodulators that stimulate the innate immune system through Toll-like receptor 9 (TLR9), offering a potential strategy for enhancing disease resistance in livestock. This study examined MsST, a class B CpG-ODN derived from Streptococcus thermophilus, a representative lactic acid bacterium widely used in yogurt production, and its role in modulating CXCL5 expression in macrophages. At a low concentration, MsST significantly enhanced CXCL5 secretion in mouse splenocytes and bone marrow-derived macrophages, outperforming other CpG-ODNs and TLR4 ligands. These effects were mediated by TLR9 and CD11b⁺ macrophages and highlighted the potential of MsST to bolster immune responses against infections. MsST strongly suppressed Abca1 in splenocytes, while the other tested CpG-ODNs increased the Abca1 levels. Although MsST may help enhance disease resistance in livestock due to potent induction of CXCL5, suppressing Abca1 raises concerns regarding lipid metabolism. The dual effects of MsST underscore the need for further research to evaluate broader implications of the utility of MsST and optimize safety and efficacy. MsST is a promising yet complex candidate for improving animal health through immunomodulation.