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Application of Immunological Methods in Personalized Medicine for the Prevention,...
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Application of Immunological Methods in Personalized Medicine for the Prevention, Diagnosis and Treatment of Intracellular Bacteria

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Clinical Medicine, Cell, and Organism Physiology".

Deadline for manuscript submissions: closed (30 March 2023) | Viewed by 11240

Special Issue Editors

Dr. Wenping Gong

E-Mail Website1 Website2
Guest Editor
Senior Department of Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, China
Interests: immunology and immunotherapy; vaccine; Mycobacterium tuberculosis
Special Issues, Collections and Topics in MDPI journals
Dr. Jun Jiao

E-Mail Website1 Website2
Guest Editor
Beijing Institute of Microbiology and Epidemiology, Beijing, China
Interests: infection; immunity and pathogenesis of intracellular bacteria such as Rickettsia

Special Issue Information

Dear Colleagues,

A small number of pathogenic bacteria mainly live inside cells, known as intracellular bacteria. There are two kinds of intracellular bacteria: obligate intracellular bacteria (e.g., Mycobacterium leprae, Pneumocystis jiroveci, Toxoplasma, Cryptosporidium, Plasmodium, Leishmania, Babesia, Coxiella burnetii, Rickettsia spp., and Trypanosoma) and facultative intracellular bacteria (Mycobacterium tuberculosis, Legionella pneumophila, Rickettsia rickettsii, Listeria monocyotogenes, Salmonella spp., Escherichia coli, Neisseria spp., Brucella spp., and Shigella spp.). Among them, Mycobacterium tuberculosis, Salmonella, Brucella, Legionella, Pneumophila, Listeria monocytogenes, Coxiella, Rickettsia, Anaplasma, and Chlamydia etc. can cause human diseases. The innate and adaptive immune systems play important roles in fighting against these intracellular bacteria. Research on the immune response of intracellular bacteria not only helps us to better understand the pathogenesis of intracellular bacteria and the immunoprotection mechanism of the host, but also lays a foundation for the discovery of new biomarkers, new vaccines and new drugs for the prevention, diagnosis and treatment of diseases caused by these bacterial infections.

In this Special Issue, recent advances and problems concerning the immunity of intracellular bacteria will be addressed. This Special Issue will include studies on immune responses to intracellular pathogen infection, immune-related biomarkers for diagnostic and prognostic assessment for infections caused by intracellular bacteria, as well as novel vaccines and vaccinology strategies against intracellular bacteria. The aim of this Special Issue is to bring together original research articles and review articles addressing new immunology strategies and tools for the diagnosis, prevention, and treatment of diseases caused by these intracellular bacteria.

Original research articles and reviews focusing on these topics will be included in this Special Issue.

Dr. Wenping Gong
Dr. Jun Jiao
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • intracellular bacteria
  • immunity
  • vaccines
  • biomarkers

Published Papers (6 papers)

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Research

12 pages, 2259 KiB  
Article
Enhancement of Immune Response of Bioconjugate Nanovaccine by Loading of CpG through Click Chemistry
by Mengting Mo, Xiang Li, Caixia Li, Kangfeng Wang, Shulei Li, Yan Guo, Peng Sun, Jun Wu, Ying Lu, Chao Pan and Hengliang Wang
J. Pers. Med. 2023, 13(3), 507; https://doi.org/10.3390/jpm13030507 - 11 Mar 2023
Cited by 2 | Viewed by 1565
Abstract
CpG is a widely used adjuvant that enhances the cellular immune response by entering antigen-presenting cells and binding with receptors. The traditional physical mixing of the antigen and CpG adjuvant results in a low adjuvant utilization rate. Considering the efficient delivery capacity of [...] Read more.
CpG is a widely used adjuvant that enhances the cellular immune response by entering antigen-presenting cells and binding with receptors. The traditional physical mixing of the antigen and CpG adjuvant results in a low adjuvant utilization rate. Considering the efficient delivery capacity of nanovaccines, we developed an attractive strategy to covalently load CpG onto the nanovaccine, which realized the co-delivery of both CpG and the antigen. Briefly, the azide-modified CpG was conjugated to a bioconjugate nanovaccine (NP-OPS) against Shigella flexneri through a simple two-step reaction. After characterization of the novel vaccine (NP-OPS-CpG), a series of in vitro and in vivo experiments were performed, including in vivo imaging, lymph node sectioning, and dendritic cell stimulation, and the results showed that more CpG reached the lymph nodes after covalent coupling. Subsequent flow cytometry analysis of lymph nodes from immunized mice showed that the cellular immune response was greatly promoted by the nanovaccine coupled with CpG. Moreover, by analyzing the antibody subtypes of immunized mice, NP-OPS-CpG was found to further promote a Th1-biased immune response. Thus, we developed an attractive method to load CpG on a nanovaccine that is simple, convenient, and is especially suitable for immune enhancement of vaccines against intracellular bacteria. Full article
(This article belongs to the Special Issue Application of Immunological Methods in Personalized Medicine for the Prevention, Diagnosis and Treatment of Intracellular Bacteria)
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13 pages, 3599 KiB  
Article
Enhancement of Cell Adhesion by Anaplasma phagocytophilum Nucleolin-Interacting Protein AFAP
by Hongcheng Tang, Daxiu Zhang, Fenfen Jiang, Lifeng Yu, Hui Tang, Jiafeng Zhu, Shuyan Wu and Hua Niu
J. Pers. Med. 2023, 13(2), 302; https://doi.org/10.3390/jpm13020302 - 8 Feb 2023
Viewed by 1635
Abstract
Anaplasma phagocytophilum, the aetiologic agent of human granulocytic anaplasmosis (HGA), is an obligate intracellular Gram-negative bacterium. During infection, A. phagocytophilum enhances the adhesion of neutrophils to the infected endothelial cells. However, the bacterial factors contributing to this phenomenon remain unknown. In this [...] Read more.
Anaplasma phagocytophilum, the aetiologic agent of human granulocytic anaplasmosis (HGA), is an obligate intracellular Gram-negative bacterium. During infection, A. phagocytophilum enhances the adhesion of neutrophils to the infected endothelial cells. However, the bacterial factors contributing to this phenomenon remain unknown. In this study, we characterized a type IV secretion system substrate of A. phagocytophilum, AFAP (an actin filament-associated Anaplasma phagocytophilum protein) and found that it dynamically changed its pattern and subcellular location in cells and enhanced cell adhesion. Tandem affinity purification combined with mass spectrometry identified host nucleolin as an AFAP-interacting protein. Further study showed the disruption of nucleolin by RNA interference, and the treatment of a nucleolin-binding DNA aptamer AS1411 attenuated AFAP-mediated cell adhesion, indicating that AFAP enhanced cell adhesion in a nucleolin-dependent manner. The characterization of cell adhesion-enhancing AFAP and the identification of host nucleolin as its interaction partner may help understand the mechanism underlying A. phagocytophilum-promoting cell adhesion, facilitating the elucidation of HGA pathogenesis. Full article
(This article belongs to the Special Issue Application of Immunological Methods in Personalized Medicine for the Prevention, Diagnosis and Treatment of Intracellular Bacteria)
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18 pages, 2817 KiB  
Article
Immunoinformatic-Based Multi-Epitope Vaccine Design for Co-Infection of Mycobacterium tuberculosis and SARS-CoV-2
by Cong Peng, Fengjie Tang, Jie Wang, Peng Cheng, Liang Wang and Wenping Gong
J. Pers. Med. 2023, 13(1), 116; https://doi.org/10.3390/jpm13010116 - 5 Jan 2023
Cited by 9 | Viewed by 2244
Abstract
(1) Background: Many co-infections of Mycobacterium tuberculosis (MTB) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have emerged since the occurrence of the SARS-CoV-2 pandemic. This study aims to design an effective preventive multi-epitope vaccine against the co-infection of MTB and SARS-CoV-2. (2) Methods: [...] Read more.
(1) Background: Many co-infections of Mycobacterium tuberculosis (MTB) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have emerged since the occurrence of the SARS-CoV-2 pandemic. This study aims to design an effective preventive multi-epitope vaccine against the co-infection of MTB and SARS-CoV-2. (2) Methods: The three selected proteins (spike protein, diacylglycerol acyltransferase, and low molecular weight T-cell antigen TB8.4) were predicted using bioinformatics, and 16 epitopes with the highest ranks (10 helper T lymphocyte epitopes, 2 CD8+ T lymphocytes epitopes, and 4 B-cell epitopes) were selected and assembled into the candidate vaccine referred to as S7D5L4. The toxicity, sensitization, stability, solubility, antigenicity, and immunogenicity of the S7D5L4 vaccine were evaluated using bioinformatics tools. Subsequently, toll-like receptor 4 docking simulation and discontinuous B-cell epitope prediction were performed. Immune simulation and codon optimization were carried out using immunoinformatics and molecular biology tools. (3) Results: The S7D5L4 vaccine showed good physical properties, such as solubility, stability, non-sensitization, and non-toxicity. This vaccine had excellent antigenicity and immunogenicity and could successfully simulate immune responses in silico. Furthermore, the normal mode analysis of the S7D5L4 vaccine and toll-like receptor 4 docking simulation demonstrated that the vaccine had docking potential and a stable reaction. (4) Conclusions: The S7D5L4 vaccine designed to fight against the co-infection of MTB and SARS-CoV-2 may be safe and effective. The protective efficacy of this promising vaccine should be further verified using in vitro and in vivo experiments. Full article
(This article belongs to the Special Issue Application of Immunological Methods in Personalized Medicine for the Prevention, Diagnosis and Treatment of Intracellular Bacteria)
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9 pages, 1534 KiB  
Article
Advanced Strategy of Trophoblasts Retrieval and Isolation from the Cervix (TRIC): Comparison of Two HLA-G Antibodies for Immunomagnetic Isolation of Trophoblasts
by Kirim Hong, Hee Yeon Jang, Sung Han Shim, Hee Young Cho and Dong Hyun Cha
J. Pers. Med. 2023, 13(1), 22; https://doi.org/10.3390/jpm13010022 - 22 Dec 2022
Cited by 2 | Viewed by 1911
Abstract
Trophoblasts retrieval and isolation from the cervix (TRIC) is a non-invasive method which enables analysis of fetal genetic information from the extravillous trophoblast cells (EVTs). The aim of this study was to compare the efficacy of the HLA-G antibodies—G233 and 4H84—in isolating EVT [...] Read more.
Trophoblasts retrieval and isolation from the cervix (TRIC) is a non-invasive method which enables analysis of fetal genetic information from the extravillous trophoblast cells (EVTs). The aim of this study was to compare the efficacy of the HLA-G antibodies—G233 and 4H84—in isolating EVT cells and provide an optimized protocol of TRIC. We analyzed EVTs from 23 pregnant women in between 5 to 20 weeks of gestation who underwent invasive prenatal testing. Two HLA-G antibodies—G233 and 4H84—were used in a subgroup of 11 and 12 samples for immunomagnetic isolation. Cells with β-hCG expression were counted to compare the rate of isolated trophoblast cells. The rate of β-hCG positive cells was significantly different between the G233 and the 4H84 by immunefluorescence microscopy (p < 0.001). The percentage of β-hCG expressing cells in G233 and 4H84 groups were 62.4 ± 8.24% and 82.6 ± 7.1%, respectively (p < 0.001). The average fetal cell positive rate was 14.1 ± 3.78 in the G233 group while it was 25.8 ± 3.9 in the 4H84 group by fluorescence in situ hybridization (FISH) (p = 0.011). Immunoisolation of trophoblast cells using 4H84 HLA-G antibody was more efficient in capturing EVT cells than using G233 for successful clinical application of TRIC. Full article
(This article belongs to the Special Issue Application of Immunological Methods in Personalized Medicine for the Prevention, Diagnosis and Treatment of Intracellular Bacteria)
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13 pages, 1604 KiB  
Article
Drug Resistance and Molecular Characteristics of Mycobacterium tuberculosis: A Single Center Experience
by Shanshan Li, Wen Chen, Mengru Feng, Yuejiao Liu and Fenghua Wang
J. Pers. Med. 2022, 12(12), 2088; https://doi.org/10.3390/jpm12122088 - 19 Dec 2022
Cited by 2 | Viewed by 1584
Abstract
In recent years, the incidence of tuberculosis (TB) and mortality caused by the disease have been decreasing. However, the number of drug-resistant tuberculosis patients is increasing rapidly year by year. Here, a total of 380 Mycobacterium tuberculosis (MTB)-positive formalin-fixed and paraffin-embedded tissue (FFPE) [...] Read more.
In recent years, the incidence of tuberculosis (TB) and mortality caused by the disease have been decreasing. However, the number of drug-resistant tuberculosis patients is increasing rapidly year by year. Here, a total of 380 Mycobacterium tuberculosis (MTB)-positive formalin-fixed and paraffin-embedded tissue (FFPE) specimens diagnosed in the Department of Pathology of the Eighth Medical Center, Chinese PLA General Hospital were collected. Among 380 cases of MTB, 85 (22.37%) were susceptible to four anti-TB drugs and the remaining 295 (77.63%) were resistant to one or more drugs. The rate of MDR-TB was higher in previously treated cases (52.53%) than in new cases [(36.65%), p  <  0.05]. Of previously treated cases, the rate of drug resistance was higher in females than in males (p  <  0.05). Among specimens obtained from males, the rate of drug resistance was higher in new cases than in previously treated cases (p  <  0.05). Of mutation in drug resistance-related genes, the majority (53/380, 13.95%) of rpoB gene carried the D516V mutation, and 13.42% (51/380) featured mutations in both the katG and inhA genes. Among the total specimens, 18.68% (71/380) carried the 88 M mutation in the rpsL gene, and the embB gene focused on the 306 M2 mutation with a mutation rate of 19.74%. Among the resistant INH, the mutation rate of −15 M was higher in resistance to more than one drug than in monodrug-resistant (p  <  0.05). In conclusion, the drug resistance of MTB is still very severe and the timely detection of drug resistance is conducive to the precise treatment of TB. Full article
(This article belongs to the Special Issue Application of Immunological Methods in Personalized Medicine for the Prevention, Diagnosis and Treatment of Intracellular Bacteria)
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14 pages, 4399 KiB  
Article
NLRP6 Induces Lung Injury and Inflammation Early in Brucella and Influenza Coinfection
by Bochang Shi, Hui Han, Huabin Li, Lingyun Tan, Xinyu Li, Keyu Wang, Bo Li, Wei He, Chongyu Tian, Fang Yan, Yanchun Shi, Yuanqiang Zheng and Zhongpeng Zhao
J. Pers. Med. 2022, 12(12), 2063; https://doi.org/10.3390/jpm12122063 - 14 Dec 2022
Cited by 1 | Viewed by 1481
Abstract
(1) Background: With the resurgence of brucellosis epidemics in China in recent years, the chances of a brucella coinfection with other common respiratory pathogens, such as the influenza virus, have increased dramatically. However, little is known about the pathogenicity or the mechanisms of [...] Read more.
(1) Background: With the resurgence of brucellosis epidemics in China in recent years, the chances of a brucella coinfection with other common respiratory pathogens, such as the influenza virus, have increased dramatically. However, little is known about the pathogenicity or the mechanisms of brucella and influenza coinfections. (2) Methods: To clarify the interventions in the early stages of lung damage due to brucella and influenza coinfections, we evaluated the effect of the coinfection on disease progression and mortality using a coinfection model in WT mice and NLRP6−/− mice, and we verified the function of NLRP6 in infection and proinflammation. (3) Results: The coinfection induced significant respiratory symptoms, weight loss, and a high mortality rate in WT mice. Influenza in the coinfection group significantly increased brucella proliferation in a synergistic manner. Meanwhile, a histological examination showed severe lung tissue destruction and excessive inflammatory responses in coinfected WT animals, and the expression of NLRP6 and IL-18 was dramatically increased in the lung tissues. Furthermore, NLRP6 deletion attenuated lung injuries and inflammation, a reduced bacterial load, and decreased IL-18 protein expression. (4) Conclusions: Our findings indicated that NLRP6 plays a critical role and might be a promising potential therapeutic target for brucella–influenza coinfections. Full article
(This article belongs to the Special Issue Application of Immunological Methods in Personalized Medicine for the Prevention, Diagnosis and Treatment of Intracellular Bacteria)
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