Abstract
Host defense peptides (HDPs) have antimicrobial and immunoregulatory activities and are involved in epithelial innate immune defense. Dietary modulation of endogenous HDP synthesis is an effective way to boost the host innate immune system. This study aimed to investigate the role of the probiotic Lactobacillus plantarum strain ZLP001 in porcine HDP induction and the underlying mechanism. To this end, we evaluated the stimulatory effect of L. plantarum ZLP001 on HDP expression in piglet intestinal tissue in vivo and porcine IPEC-J2 cells and 3D4/31 cells in vitro, and we examined the underlying intracellular signaling pathway in IPEC-J2 cells. L. plantarum ZLP001 treatment increased the mRNA expression of jejunal and ileal HDPs in weaned piglets. In IPEC-J2 and 3D4/31 cells, L. plantarum ZLP001 stimulated HDP expression, but different HDP induction patterns were observed, with the various HDPs exhibiting different relative mRNA levels in each cell line. L. plantarum ZLP001 induced porcine HDP expression through toll-like receptor (TLR)2 recognition as evidenced by the fact that HDP expression was suppressed in TLR2-knockdown IPEC-J2 cells. Furthermore, we found that L. plantarum ZLP001 activated the extracellular signal-regulated kinase (ERK)1/2 and c-jun N-terminal kinase (JNK) signaling pathways, as indicated by enhanced phosphorylation of both ERK1/2 and JNK and the fact that HDP expression was suppressed upon inhibition of ERK1/2 and JNK. Furthermore, L. plantarum ZLP001 activated c-fos and c-jun transcription factor phosphorylation and activity. We conclude that L. plantarum ZLP001 induces porcine HDP expression in vivo and in vitro, and the induction seems to be regulated via TLR2 as well as the ERK1/2/JNK and c-jun/c-fos signaling pathways. Modulation of endogenous HDPs mediated by L. plantarum ZLP001 might be a promising approach to improving intestinal health and enhancing diarrhea resistance in weaning piglets.
Highlights
Weaning stress in piglets can suppress immune responses, rendering the piglets vulnerable to infectious diseases, including diarrhea [1]
We demonstrated that Lactobacillus plantarum ZLP001, which we isolated from healthy piglet ileal mucosa [16], exert beneficial effects on growth performance and antioxidant status in weaning piglets [17], can upregulate the expression of Host defense peptides (HDPs) in IPEC-J2 cells but did not trigger an inflammatory response [18]
L. plantarum ZLP001 was administered to weaned piglets at 2 g/kg diet for 28 days to determine whether it affects HDP expression in intestinal tissues. mRNA expression of six porcine HDPs, including pBD2, pBD3, PG1–5, pEP2C, pBD114, and pBD129, was evaluated by RT-qPCR (Figure 1)
Summary
Weaning stress in piglets can suppress immune responses, rendering the piglets vulnerable to infectious diseases, including diarrhea [1]. The overuse of antibiotics has led to the development of antimicrobial-resistant bacterial strains, which threaten animal as well as human health. HDPs are activated in response to the oscillating energy status of cells and tissues and help maintain and enhance defensive barriers without causing damage or inflammation [8]. Certain nutritional components, such as VD3, butyrate, and zinc, induce HDP gene expression in animals, and humans without causing inflammatory damage [9,10,11]. The extent of modulation could be varied in different models and among different strains [15]
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