Recombinant plasmids containing CpG with porcine host defense peptides (PR-39/pBD-1) modulates the innate and adaptive intestinal immune responses (including maternal-derived) in piglets

Zhang, Shuxia; Cai, Hao; Cao, Ding; Deng, Jinbo; Jia, Junhao; Li, Jiaoqing; Ming, Feiping; Zhao, Peijing; Ma, Miaopeng; Liang, Qiao‐Mei; Zeng, Min; Zhang, Linghua

doi:10.1016/j.intimp.2019.03.007

Cited by 4 publications

(8 citation statements)

References 18 publications

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“…Moreover, IFN-γ, mainly secreted by Th1 cells and natural killer cells, implicates innate immune responses [ 52 , 53 ], and IL-1β is a proinflammatory cytokine involved in the activation of macrophages and epithelial cells [ 54 , 55 ]. By treating the chicken lymphocytes with LACpG10-HL, we obtained upregulated expressions of these cytokines, further confirming that LACpG10-HL exerted an immunostimulatory effect on the lymphocytes, consistent with our previous findings [ 23 , 56 ].…”

Section: Discussionsupporting

confidence: 92%

“…Since IFN-γ and IL-12 are Th1 cytokines acting in the Th1 immune responses, which is beneficial for preventing infections [ 54 , 57 ], our results displaying the upregulated level of these cytokines were in correspondence with the above data of bacterial invasion, phagocytosis, and clearance. Moreover, our former findings reported that the sustained upregulation of IFN-γ was advantageous to bacterial clearance [ 11 , 23 ]. Furthermore, in animals, IL-12 can activate the natural killer cells to produce IFN-γ, while in return, IFN-γ can activate macrophages to produce IL-12, so a self-amplifying loop is formed [ 58 , 59 ].…”

Section: Discussionmentioning

confidence: 99%

“…The plasmid pNZ8148 was stored in our laboratory ( Table S1 ). Recombinant plasmid pNZ8148-CpG10 was constructed through the insertion of CpG10 [ 23 ] from the pre-synthesized pUC19-CpG10 into the Xba I and Sac I restriction sites of pNZ8148 ( Figure S2 ). The two plasmids, pNZ8148 and pNZ8148-CpG10, were transformed into E. coli MC1061 for amplification.…”

Section: Methodsmentioning

confidence: 99%

“…In this study, six kinds of bacteria, including Lactococcus lactis subsp. Cremoris NZ9000, Escherichia coli MC1061, Pseudomonas aeruginosa ATCC 27853 ( P. aeruginosa ), Shigella sonnei CMCC 51592 ( S. sonnei ), Enterohemorrhagic Escherichia coli ATCC 35150 (EHEC) and Streptococcus pyogenes ATCC 19615 ( S. pyogenes ) [ 23 ], were preserved in our laboratory ( Table S1 ). Moreover, three kinds of cells were used in this study, including HD11, IPEC-J2, and chicken lymphocytes ( Table S1 ).…”

Section: Methodsmentioning

confidence: 99%

“…Fortunately, suitable CpG-united agents with superior efficacy in curing cancers have been considered by Karapetyan et al [ 22 ], inspiring us to seek CpG-united agents to implement the similar role as antibiotics. To meet the demand for highly efficient production, we selected the CpG plasmids, replicating independently in bacteria, as CpG formulation in this study, whose CpG-ODNs-like performances had been confirmed in our previous study [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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LACpG10-HL Functions Effectively in Antibiotic-Free and Healthy Husbandry by Improving the Innate Immunity

Pan

Zhao

et al. 2022

IJMS

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Antibiotics are broadly restricted in modern husbandry farming, necessitating the need for efficient and low-cost immunomodulatory preparations in antibiotic-free and healthful farming. As is known to all, CpG oligonucleotides (CpG-ODNs, an effective innate immunostimulatory agent) recognized by TLR9 in mammals (while TLR21 in avians) could collaborate with some united agent to induce stronger immune responses, but the cost is prohibitively expensive for farmers. Here, considering the coordination between TLR2 and TLR9/TLR21, we firstly proposed the idea that the well-fermented Lactococcus lactis could be utilized as a CpG-plasmid carrier (LACpG10) to enhance the host's innate immunity against pathogenic invasion. In the present study, after obtaining LACpG10-HL from homogenized and lyophilized recombinant strain LACpG10, we treated primary chicken lymphocytes, two cell lines (HD11 and IPEC-J2), and chickens with LACpG10-HL, CpG plasmids (pNZ8148-CpG10), and other stimulants, and respectively confirmed the effects by conducting qRT-PCR, bacterial infection assays, and a zoological experiment. Our data showed that LACpG10-HL could induce excellent innate immunity by regulating autophagy reactions, cytokine expression, and motivating PRRs. Interestingly, despite having no direct antiseptic effect, LACpG10-HL improved the antibacterial capacities of lymphocytes and enterocytes at the first line of defense. Most importantly, water-supplied LACpG10-HL treatment reduced the average adverse event rates, demonstrating that LACpG10-HL maintained its excellent immunostimulatory and protective properties under farming conditions. Our research not only contributes to revealing the satisfactory effects of LACpG10-HL but also sheds new light on a cost-effective solution with optimal immune effects in green, antibiotic-free, and healthful husbandry farming.

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