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Immune Response Regulation in Animals

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A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 12818

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Prof. Dr. Rong Gao

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Guest Editor

School of Life Sciences, Sichuan University, Chengdu 610017, China
Interests: immunoregulation of animals; adjuvant for vaccine; immune memory; cytokine; biotechnology; molecular genetics

Prof. Dr. Hua-Ji Qiu

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Guest Editor

Harbin Veterinary Research Institute (HVRI), Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China
Interests: classical swine fever; African swine fever; pseudorabies; vaccines; innate and adaptive immunity; virus-host interactions; pathogenesis; diagnostic assays
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Dear Colleagues,

(1) outline the overall a. focus, b. scope and c. purpose of the special issue

Immune response regulation is increasingly important, not only for vaccinating animals but also for infectious diseases which do not currently have a vaccine. Newly emerging pathogens and immunosuppression complications continue to threaten the health of human beings and animals around the world. Therefore, there is an urgent need to explore and develop safer and more effective immunomodulators, enhancing animals’ immunity and resistance to diseases.

Besides adjuvants, immunomodulator innovation is also popular for some infectious diseases that can not be prevented via vaccine. Generally, immunomodulator could enhance the magnitude, breadth, and durability of animals’ immune response to different antigens or pathogens. Recent basic advances indicate that tissue damage, different forms of cell death, and metabolic and nutrient sensors could be employed to modulate the innate immune system to activate adaptive immunity. Moreover, novel conceptual discoveries in systems biology highlight the molecular networks driving immune response to vaccines, providing mechanistic insights and guidance to speed up the immunomodulator discovery and development process. This will satisfy the urgent need to control new emerging infectious diseases, such as COVID-19 and tuberculosis.

(2) suggest how the issue will usefully supplement (relate to) existing literature

The goal of this Research Topic on immune-response regulation is to provide a forum to promote the academic exchange of research on the regulation of activation of innate immunity, adaptive immune response process, immune memory, and immunoprotection of animals and humans to vaccination or infection by different molecules. It focuses on revealing how to explore the novel immunomodulators, discussing their potential effects on vaccinations and infections, and highlighting how to develop safer and more competent immunomodulators to control infectious diseases in a better, more cost-effective way. Based on the latest immunology advances and system vaccinology, we welcome manuscripts related to the following subtopics:

Stimulation of immune cells by new molecules from the Danger model and their derivatives, including agonists of PRRs, damage-associated molecular patterns (DAMPs), and cell death via necroptosis or pyroptosis, as well as other stress signals such as amino acid starvation (via ancient stress and nutrient-sensing pathways).
The possible synergic effects among these stimuli on Toll-like receptors (TLRs), innate PRRs (such as retinoic acid-inducible gene I (RIG-I), and other RNA sensors), DNA sensors (such as stimulator of interferon genes (STING) protein), C-type lectins, nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and cytosolic receptors such as NLRP3.
Approaches of targeting DCs/APCs to promote uptake of antigens, activation of adaptive competent immune cells via different routes or molecules, such as FcR and mannose receptors, etc.
Use of the molecular networks and insights from systems vaccinology acquire more accurate and comprehensive regulation of innate and adaptive immune responses to result in stronger immunity and longer protection duration, such as cytokines, designing novel metabolites, small molecules immune potentiators (SMIPs) and synthetic ligands allowing targeting subsets of adaptive competent immune cells and precision modulation and orchestrating continuous education to B and T cells, which lead to better proliferation, differentiation, and maturation of immune memory and effectors to induce sustained protective immunity.

In summation, we hope that more immunomodulators will be discovered and invented to regulate the immunity of animals, facilitating the prevention and control of various diseases in the future and helping people to eliminate pathogenic challenges.

Prof. Dr. Rong Gao
Prof. Dr. Hua-Ji Qiu
Guest Editors

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Keywords

immunoregulation of animals
vaccination
immunomodulators
immune memory
cytokine
biotechnology
immune response
molecular networks

Published Papers (8 papers)

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Research

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17 pages, 316 KiB

Open AccessArticle

Dietary Artemisia Ordosica Polysaccharide Enhances Spleen and Intestinal Immune Response of Broiler Chickens

by Haidong Du, Yuanyuan Xing, Yuanqing Xu, Xiao Jin, Sumei Yan and Binlin Shi

Biology 2023, 12(11), 1390; https://doi.org/10.3390/biology12111390 - 31 Oct 2023

Viewed by 1059

Abstract

The spleen and small intestines are the primary immune organs that provide important immunity against various diseases. Artemisia ordosica polysaccharide (AOP) could be used as an immunologic enhancer to boost immunity in response to infection. This study was performed to explore the effects of the dietary supplementation of AOP on the growth performance and spleen and small intestine immune function in broilers. A total of 288 AA broilers (1 day old) were randomly assigned into six dietary groups. Each group included six replicates of eight broilers per cage. The broilers were fed with a basal diet supplemented with 0 mg/kg (CON), 50 mg/kg chlortetracycline (CTC), 250, 500, 750, and 1000 mg/kg AOP for 42 d. The results showed that dietary AOP supplementation affected broiler growth performance, with 750 and 1000 mg/kg of AOP being able to significantly improve broiler BWG, and 750 mg/kg of AOP was able to significantly reduce the FCR. The dietary AOP supplementation increased the levels of IgA, IgG, IgM, IL-1β, IL-2, and IL-4 in the spleen and small intestine in a dose-dependent manner (p < 0.05). Meanwhile, we found that AOP can promote the mRNA expression of TLR4/MAPK/NF-κB signaling-pathway-related factors (TLR4, MyD88, P38 MAPK, JNK, NF-κB p50, and IL-1β). In addition, the dietary supplementation of 750 mg/kg AOP provides better immunity in the tissue than the CON group but showed no significant difference from the CTC group. Therefore, AOP has an immunoregulatory action and can modulate the immune function of broilers via the TLR4/ NF-ΚB/MAPK signal pathway. In conclusion, dietary supplementation with 750 mg/kg AOP may be alternatives to antibiotics for enhancing broilers’ health, immunity, and growth performance. Full article

(This article belongs to the Special Issue Immune Response Regulation in Animals)

16 pages, 2451 KiB

Open AccessArticle

Nlrp3 Deficiency Alleviates Lipopolysaccharide-Induced Acute Kidney Injury via Suppressing Renal Inflammation and Ferroptosis in Mice

by Zhilan Li, Xuan Wang, Yi Peng, Hongling Yin, Shenyi Yu, Weiru Zhang and Xin Ni

Biology 2023, 12(9), 1188; https://doi.org/10.3390/biology12091188 - 31 Aug 2023

Cited by 1 | Viewed by 1355

Abstract

The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is a vital component of many inflammatory responses. Here, we intended to investigate the involvement of NLRP3 in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (S-AKI) and explore its mechanisms. For the first time, we validated elevated NLRP3 expression in the renal tissues of S-AKI patients by immunohistochemistry analysis. Through LPS injection in both wild-type and Nlrp3^−/− mice, a S-AKI model was developed. It was found that LPS-induced kidney injury, including an abnormal morphology in a histological examination, abnormal renal function in a laboratory examination, and an increase in the expression of AKI biomarkers, was dramatically reversed in Nlrp3-deficient mice. Nlrp3 deletion alleviated renal inflammation, as evidenced by the suppression of the expression of pro-inflammatory cytokines and chemokines. A combinative analysis of RNA sequencing and the FerrDb V2 database showed that Nlrp3 knockout regulated multiple metabolism pathways and ferroptosis in LPS-induced S-AKI. Further qPCR coupled with Prussian blue staining demonstrated that Nlrp3 knockout inhibited murine renal ferroptosis, indicating a novel mechanism involving S-AKI pathogenesis by NLRP3. Altogether, the aforementioned findings suggest that Nlrp3 deficiency alleviates LPS-induced S-AKI by reducing renal inflammation and ferroptosis. Our data highlight that NLRP3 is a potential therapeutic target for S-AKI. Full article

(This article belongs to the Special Issue Immune Response Regulation in Animals)

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15 pages, 5828 KiB

Open AccessArticle

Expression Improvement of Recombinant Plasmids of the Interleukin-7 Gene in Chitosan-Derived Nanoparticles and Their Elevation of Mice Immunity

by Wenli Hou, Linhan Zhang, Jianlin Chen, Yiren Gu, Xuebin Lv, Xiuyue Zhang, Jiangling Li, Hui Liu and Rong Gao

Biology 2023, 12(5), 667; https://doi.org/10.3390/biology12050667 - 28 Apr 2023

Cited by 1 | Viewed by 1580

Abstract

To investigate a safe and effective approach for enhancing the in vivo expression of recombinant genes and improving the systemic immunity of animals against infectious diseases, we employed the interleukin-7 (IL-7) gene from Tibetan pigs to construct a recombinant eukaryotic plasmid (VRTPIL-7). We first examined VRTPIL-7’s bioactivity on porcine lymphocytes in vitro and then encapsulated it with polyethylenimine (PEI), chitosan copolymer (CS), PEG-modified galactosylated chitosan (CS-PEG-GAL) and methoxy poly (ethylene glycol) (PEG) and PEI-modified CS (CS-PEG-PEI) nanoparticles using the ionotropic gelation technique. Next, we intramuscularly or intraperitoneally injected mice with various nanoparticles containing VRTPIL-7 to evaluate their immunoregulatory effects in vivo. We observed a significant increase in neutralizing antibodies and specific IgG levels in response to the rabies vaccine in the treated mice compared to the controls. Treated mice also exhibited increased leukocytes, CD8+ and CD4+ T lymphocytes, and elevated mRNA levels of toll-like receptors (TLR1/4/6/9), IL-1, IL-2, IL-4, IL-6, IL-7, IL-23, and transforming growth factor-beta (TGF-β). Notably, the recombinant IL-7 gene encapsulated in CS-PEG-PEI induced the highest levels of immunoglobulins, CD4+ and CD8+ T cells, TLRs, and cytokines in the mice’s blood, suggesting that chitosan-PEG-PEI may be a promising carrier for in vivo IL-7 gene expression and enhanced innate and adaptive immunity for the prevention of animal diseases. Full article

(This article belongs to the Special Issue Immune Response Regulation in Animals)

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17 pages, 2581 KiB

Open AccessArticle

Immunomodulatory Effects of Bacterial Toll-like Receptor Ligands on the Phenotype and Function of Milk Immune Cells in Dromedary Camel

by Jamal Hussen, Mayyadah Abdullah Alkuwayti, Baraa Falemban, Mohammed Ali Al-Sukruwah, Sameer M. Alhojaily, Naser Abdallah Al Humam and Salma Al Adwani

Biology 2023, 12(2), 276; https://doi.org/10.3390/biology12020276 - 09 Feb 2023

Cited by 3 | Viewed by 1572

Abstract

(1) Toll-like receptors (TLR) are a family of pattern recognition receptors that sense distinct molecular patterns of microbial origin. Although the immune cell composition of camel milk has been recently described, host–pathogen interaction studies in the camel mammary gland are still scarce. The present study aimed to use a whole milk stimulation assay for investigating the modulatory effect of selected Toll-like receptor (TLR) ligands on the phenotype and function of milk immune cells. (2) Methods—camel milk samples (n = 7) were stimulated in vitro with the TLR4 ligand LPS or the TLR2/1 ligand Pam3CSK4, and separated milk cells were evaluated for stimulation-induced shape change, the expression of cell surface markers, phagocytosis, apoptosis, ROS production, and NETosis. Stimulation with PMA was used as a control stimulation. (3) Results—all stimulants induced shape change in milk cells, change in the expression of several cell markers, and increased cell apoptosis and NETosis. In addition, stimulation with Pam3CSK4 and PMA was associated with enhanced ROS production, while only PMA stimulation resulted in enhanced bacterial phagocytosis by milk immune cells. (4) Conclusions—our data indicates selective modulating effects of the TLR ligands LPS and Pam3CSK4 on camel milk phagocytes. These results may have implications for the use of synthetic TLR agonists as immunomodulatory adjuvants of the immune response to intra-mammary vaccines against mastitis pathogens. Full article

(This article belongs to the Special Issue Immune Response Regulation in Animals)

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14 pages, 3363 KiB

Open AccessArticle

Porcine Interleukin-17 and 22 Co-Expressed by Yarrowia lipolytica Enhance Immunity and Increase Protection against Bacterial Challenge in Mice and Piglets

by Junjie Peng, Fang Yang, Jianlin Chen, Shaohua Guo, Linhan Zhang, Dinghao Deng, Jiangling Li, Xuebin Lv and Rong Gao

Biology 2022, 11(12), 1747; https://doi.org/10.3390/biology11121747 - 30 Nov 2022

Viewed by 1543

Abstract

Drug resistance in economic animals to pathogens is a matter of widespread concern due to abuse of antibiotics. In order to develop a safe and economical immunopotentiator to raise the immunity and antibacterial response as a replacement for antibiotics, a recombinant yeast co-expressing pig interleukin-17 (IL-17) and IL-22 was constructed and designated as Po1h-pINA1297-IL-17/22. To evaluate the immunoregulator activities of Po1h-pINA1297-IL-17/22, two experiment groups (oral inoculation with Po1h-pINA1297 or Po1h-pINA1297-IL-17/22) and a negative control group (PBS) were set up using 4-week-old female BALB/c mice (10/group). The level of cytokines, including IL-2, IL-4, IL-10, and IFN-γ, were detected by ELISA, and the circulating CD4+ and CD8+ lymphocytes were quantified by flow cytometry. The IgG and secretory IgA (SIgA) levels in both small intestine and fecal matter were also measured by ELISA. The results indicated that the IgG antibody titer and SIgA concentration increased significantly in the Po1h-pINA1297-IL17/22 group in comparison with the controls (p < 0.05) and so did the cytokine levels in the serum (IL-2, IL-4, IL-10, and IFN-γ). In addition, CD4+ and CD8+ T cells were also obviously elevated in the Po1h-pINA1297-IL17/22 group on 35th day (p < 0.05). After challenge with pathogenic Salmonella typhimurium, the Po1h-pINA1297-IL17/22 group showed a relatively higher survival rate without obvious infectious symptoms. On the contrary, the mortality of control group reached 80% due to bacterial infection. As for the piglet experiment, 30 healthy 7-day piglets were similarly attributed into three groups. The oral inoculation of piglets with Po1h-pINA1297-IL17/22 also markedly improved the growth performance and systemic immunity (up-regulations of IL-4, IL-6, IL-15, IL-17, IL-22, and IL-23). Overall, the results indicated that Po1h-pINA1297-IL17/22 effectively promoted the humoral and cellular immunity against bacterial infection. These proved the promising potential of Po1h-pINA1297-IL-17/22 to be a potent immunopotentiator for the prevention of microbial pathogen infections. Full article

(This article belongs to the Special Issue Immune Response Regulation in Animals)

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17 pages, 4669 KiB

Open AccessArticle

Co-Expression of Pig IL-2 and Fusion Bovine Cathelicidin Gene by Recombinant Plasmids in Yeast and Their Promotion of Mouse Antibacterial Defense

by Jianlin Chen, Junjie Peng, Changjun Ma, Linhan Zhang, Xueyin Wu, Hong Wei, Jianglin Li, Xuebin Lü and Rong Gao

Biology 2022, 11(10), 1491; https://doi.org/10.3390/biology11101491 - 12 Oct 2022

Cited by 1 | Viewed by 1415

Abstract

In order to develop an effective and safe immunomodulator to enhance the antimicrobial bioactivity and immunity of animals against infectious bacterial diseases, a recombinant plasmid pGAPZαA-IL2-B co-expressing pig interleukin-2 (PIL-2) and fused bovine cathelicidin (FBC) genes were constructed using the 2A self-cleavage technique. After being expressed in Pichia pastoris strain SMD1168, the recombinant yeast was administered orally to 5-week-old female ICR mice. The control mice were similarly dosed with P. pastoris with a blank plasmid or FBC recombinant plasmid alone. At 28 days post-treatment, the mice were challenged intraperitoneally with virulent strains of either E. coli or S. aureus. Compared with the control groups, the mice that received recombinant yeast co-expressing PIL-2/FBC manifested significant increases in the number of leukocytes, CD4+ and CD8+ T cells, IgG, and the gene expressions of TLRs(TLR1,4,6,9), antimicrobial peptides(CRP4 and CRAMP) and cytokines (IL-2, 4, 6, 7, 12, 15, 23, IFN-γ, and TNF-α) in the blood. Furthermore, the treated mice displayed significantly higher survival than the other two control groups after the challenge. These results suggest that the antimicrobial activity and immunity of animals can be effectively enhanced by the in vivo co-expression of IL-2 and the FBS gene, which can facilitate the development of new immunopotentiation molecules to overcome the infection of antibiotic-resistant bacteria. Full article

(This article belongs to the Special Issue Immune Response Regulation in Animals)

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12 pages, 2299 KiB

Open AccessArticle

Characterization of Porcine Monocyte-Derived Macrophages Cultured in Serum-Reduced Medium

by Hana Štěpánová, Lenka Kavanová, Lenka Levá, Monika Vícenová, Kamil Šťastný and Martin Faldyna

Biology 2022, 11(10), 1457; https://doi.org/10.3390/biology11101457 - 04 Oct 2022

Viewed by 1605

Abstract

The aim of this study was to establish a cell culture system for the generation of porcine monocyte-derived macrophages (MDMs) under reduced-serum conditions. Cultures based on either the Nu-Serum™ Growth Medium Supplement (NUS) or a conventional fetal bovine serum (FBS) were compared, which included the assessment of FBS from two different providers (FBS1 and FBS2). The data obtained confirmed the significant impact of culture conditions on in vitro-generated MDMs. The MDMs cultured under reduced-serum conditions showed increased levels of IL-1β and CD86 mRNA and a proinflammatory cytokine profile, characterized by the increased mRNA expression of IL-23p19, CXCL10, and CCL5. Phagocytic and respiratory burst activities were not adversely affected. Surprisingly, the difference between the two FBSs was much more pronounced than the effect of the reduced-serum supplement. The FBS1 culture conditions gave rise to macrophages with higher surface levels of CD14, CD16, and CD163, a lower CD80 mRNA expression, and an increased induction of IL-10 gene expression. In contrast, none of these trends were observed in macrophage cultures supplemented with FBS2. Instead, the FBS2 culture showed increased levels of IL-1b and CD86 mRNA. In conclusion, reduced-serum culture is a useful tool for in vitro porcine MDM generation, in line with the current research trend of reducing FBS use in biological research. Full article

(This article belongs to the Special Issue Immune Response Regulation in Animals)

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Review

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20 pages, 572 KiB

Open AccessReview

Fishing Innate Immune System Properties through the Transcriptomic Single-Cell Data of Teleostei

by Aleksandr V. Bobrovskikh, Ulyana S. Zubairova and Alexey V. Doroshkov

Biology 2023, 12(12), 1516; https://doi.org/10.3390/biology12121516 - 12 Dec 2023

Viewed by 1685

Abstract

The innate immune system is the first line of defense in multicellular organisms. Danio rerio is widely considered a promising model for IIS-related research, with the most amount of scRNAseq data available among Teleostei. We summarized the scRNAseq and spatial transcriptomics experiments related to the IIS for zebrafish and other Teleostei from the GEO NCBI and the Single-Cell Expression Atlas. We found a considerable number of scRNAseq experiments at different stages of zebrafish development in organs such as the kidney, liver, stomach, heart, and brain. These datasets could be further used to conduct large-scale meta-analyses and to compare the IIS of zebrafish with the mammalian one. However, only a small number of scRNAseq datasets are available for other fish (turbot, salmon, cavefish, and dark sleeper). Since fish biology is very diverse, it would be a major mistake to use zebrafish alone in fish immunology studies. In particular, there is a special need for new scRNAseq experiments involving nonmodel Teleostei, e.g., long-lived species, cancer-resistant fish, and various fish ecotypes. Full article

(This article belongs to the Special Issue Immune Response Regulation in Animals)

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