Yunjie Du

Lanzhou University

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Pu He

Lanzhou University

Bingdong Zhu

Lanzhou University

Fei Li

Ministry of Education of the People's Republic of China

Qianqian Cao

Lanzhou University

Hongxia Niu

Zhejiang Chinese Medical University

Ying Zhang

First Affiliated Hospital Zhejiang University

Lei Jiao

Lanzhou Institute of Husbandry and Pharmaceutical Sciences

Lina Hu

Dalian Medical University

Dandan Chen

Southern Medical University

Zhuoxuan Lv

Zhejiang Chinese Medical University

Cooperative Institutions

Lanzhou University

Zhejiang Chinese Medical University

Chinese Academy of Agricultural Sciences

Zhejiang University

Lanzhou Veterinary Research Institute

Chinese Academy of Sciences

Lanzhou Institute of Husbandry and Pharmaceutical Sciences

First Affiliated Hospital Zhejiang University

Johns Hopkins University

Yunnan University

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The adjuvant effect of manganese on tuberculosis subunit vaccine Bfrb-GrpE

npj Vaccines (2024)

Shuai Zhou Qianqian Cao Zunjing Zhang Yunjie Du Yilin Hou

Protein subunit vaccines, lacking pathogen-associated molecular patterns that trigger immune responses, rely on adjuvants to induce robust immune responses against the target pathogen. Thus, selection of adjuvants plays a crucial role in the design of protein subunit vaccines. Recently, there has been growing interest in utilizing cGAS-STING agonists as vaccine adjuvants. In this study, we investigated the adjuvant effect of manganese (Mn), a cGAS-STING agonist, on the tuberculosis subunit vaccine Bfrb-GrpE (BG) in a mouse model. Initially, mice were administered with BG-Mn(J), and its immunogenicity and protective efficacy were assessed six weeks after the final immunization. The results showed that Mn(J) enhanced both the cellular and humoral immune responses to the BG vaccine and conferred effective protection against M. tuberculosis H37Ra infection in mice, leading to a significant reduction of 2.0 ± 0.17 Log10 CFU in spleens and 1.3 ± 0.17 Log10 CFU in lungs compared to the PBS control group. Additionally, we assessed the BG-Mn(J) vaccine in a surrogate model of tuberculosis in rabbit skin model. The vaccination with BG-Mn(J) also provided effective protection in the rabbit model, as indicated by a decreased bacterial load at the infection site, minimal pathological damage, and accelerated healing. These findings suggest that Mn(J) holds promise as an adjuvant for tuberculosis vaccines, underscoring its potential to enhance vaccine efficacy and offer protection against tuberculosis infection.

Tuberculosis vaccines

10.1038/s41541-024-01049-x

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Possible Mechanisms of Lymphopenia in Severe Tuberculosis

Microorganisms (2023)

Fei Li Dandan Chen Zeng Qingqing Yunjie Du

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis). In lymphopenia, T cells are typically characterized by progressive loss and a decrease in their count results. Lymphopenia can hinder immune responses and lead to systemic immunosuppression, which is strongly associated with mortality. Lymphopenia is a significant immunological abnormality in the majority of patients with severe and advanced TB, and its severity is linked to disease outcomes. However, the underlying mechanism remains unclear. Currently, the research on the pathogenesis of lymphopenia during M. tuberculosis infection mainly focuses on how it affects lymphocyte production, survival, or tissue redistribution. This includes impairing hematopoiesis, inhibiting T-cell proliferation, and inducing lymphocyte apoptosis. In this study, we have compiled the latest research on the possible mechanisms that may cause lymphopenia during M. tuberculosis infection. Lymphopenia may have serious consequences in severe TB patients. Additionally, we discuss in detail potential intervention strategies to prevent lymphopenia, which could help understand TB immunopathogenesis and achieve the goal of preventing and treating severe TB.

Immunosuppression

Pathogenesis

Lymphocytopenia

Immune Dysfunction

10.3390/microorganisms11112640

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Construction and evaluation of a novel multi-antigenic Mycobacterium tuberculosis subunit vaccine candidate BfrB-GrpE/DPC

International Immunopharmacology (2023)

Hongxia Niu Qianqian Cao Tingting Zhang Yunjie Du Pu He

10.1016/j.intimp.2023.111060

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Nanoparticle-Based Immunotherapy for Reversing T-Cell Exhaustion

International Journal of Molecular Sciences (2024)

Fei Li Y J Wang Dandan Chen Yunjie Du

T-cell exhaustion refers to a state of T-cell dysfunction commonly observed in chronic infections and cancer. Immune checkpoint molecules blockading using PD-1 and TIM-3 antibodies have shown promising results in reversing exhaustion, but this approach has several limitations. The treatment of T-cell exhaustion is still facing great challenges, making it imperative to explore new therapeutic strategies. With the development of nanotechnology, nanoparticles have successfully been applied as drug carriers and delivery systems in the treatment of cancer and infectious diseases. Furthermore, nanoparticle-based immunotherapy has emerged as a crucial approach to reverse exhaustion. Here, we have compiled the latest advances in T-cell exhaustion, with a particular focus on the characteristics of exhaustion that can be targeted. Additionally, the emerging nanoparticle-based delivery systems were also reviewed. Moreover, we have discussed, in detail, nanoparticle-based immunotherapies that aim to reverse exhaustion, including targeting immune checkpoint blockades, remodeling the tumor microenvironment, and targeting the metabolism of exhausted T cells, etc. These data could aid in comprehending the immunopathogenesis of exhaustion and accomplishing the objective of preventing and treating chronic diseases or cancer.

Cancer Immunotherapy

Reversing

Cancer Treatment

10.3390/ijms25031396

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Glutamate Transporters GltS, GltP and GltI Are Involved in Escherichia coli Tolerance In Vitro and Pathogenicity in Mouse Urinary Tract Infections

Microorganisms (2023)

Hongxia Niu Tuodi Li Yunjie Du Zhuoxuan Lv Qianqian Cao

To verify the roles of GltS, GltP, and GltI in E. coli tolerance and pathogenicity, we quantified and compared the relative abundance of gltS, gltP, and gltI in log-phase and stationary-phase E. coli and constructed their knockout mutant strains in E. coli BW25113 and uropathogenic E. coli (UPEC) separately, followed by analysis of their abilities to tolerate antibiotics and stressors, their capacity for adhesion to and invasion of human bladder epithelial cells, and their survival ability in mouse urinary tracts. Our results showed that gltS, gltP, and gltI transcripts were higher in stationary phase E. coli than in log-phase incubation. Furthermore, deletion of gltS, gltP, and gltI genes in E. coli BW25113 results in decreased tolerance to antibiotics (levofloxacin and ofloxacin) and stressors (acid pH, hyperosmosis, and heat), and loss of gltS, gltP, and gltI in uropathogenic E. coli UTI89 caused attenuated adhesion and invasion in human bladder epithelial cells and markedly reduced survival in mice. The results showed the important roles of the glutamate transporter genes gltI, gltP, and gltS in E. coli tolerance to antibiotics (levofloxacin and ofloxacin) and stressors (acid pH, hyperosmosis, and heat) in vitro and in pathogenicity in mouse urinary tracts and human bladder epithelial cells, as shown by reduced survival and colonization, which improves our understanding of the molecular mechanisms of bacterial tolerance and pathogenicity.

Multidrug tolerance

10.3390/microorganisms11051173

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Tuberculosis Vaccines and T Cell Immune Memory

Vaccines (2024)

Fei Li Wenrui Dang Yunjie Du Xiaonan Xu Pu He

Tuberculosis (TB) remains a major infectious disease partly due to the lack of an effective vaccine. Therefore, developing new and more effective TB vaccines is crucial for controlling TB.

Immunological memory

Tuberculosis vaccines

Memory T cell

10.3390/vaccines12050483

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Unraveling the Immune Regulatory Functions of USP5: Implications for Disease Therapy

Biomolecules (2024)

Jinyi Gu Changshun Chen Pu He Yunjie Du Bingdong Zhu

Ubiquitin-specific protease 5 (USP5) belongs to the ubiquitin-specific protease (USP) family, which uniquely recognizes unanchored polyubiquitin chains to maintain the homeostasis of monoubiquitin chains. USP5 participates in a wide range of cellular processes by specifically cleaving isopeptide bonds between ubiquitin and substrate proteins or ubiquitin itself. In the process of immune regulation, USP5 affects important cellular signaling pathways, such as NF-κB, Wnt/β-catenin, and IFN, by regulating ubiquitin-dependent protein degradation. These pathways play important roles in immune regulation and inflammatory responses. In addition, USP5 regulates the activity and function of immunomodulatory signaling pathways via the deubiquitination of key proteins, thereby affecting the activity of immune cells and the regulation of immune responses. In the present review, the structure and function of USP5, its role in immune regulation, and the mechanism by which USP5 affects the development of diseases by regulating immune signaling pathways are comprehensively overviewed. In addition, we also introduce the latest research progress of targeting USP5 in the treatment of related diseases, calling for an interdisciplinary approach to explore the therapeutic potential of targeting USP5 in immune regulation.

Deubiquitinating enzyme

10.3390/biom14060683

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The combination of Mycobacterium tuberculosis fusion proteins LT33 and LT28 induced strong protective immunity in mice

Frontiers in Immunology (2024)

Pu He Juan Wang D. S. K. Tan Lina Hu Yanlin Ma

Effective subunit vaccines for tuberculosis (TB) must target antigenic components at various stages of infection. In this study, we constructed fusion proteins using secreted antigens from Mycobacterium tuberculosis ( M. tuberculosis ), specifically ESAT6, CFP10, MPT64, and Rv2645 from the proliferation stage, along with latency-associated antigens Rv1738 and Rv1978. The resulting fusion proteins, designated LT33 (ESAT6-CFP10-Rv1738) and LT28 (MPT64 61-170 -Rv1978 8-60 -Rv2645 21-80 ), were combined with an adjuvant containing dimethyldioctadecylammonium bromide (DDA), polyriboinosinic polyribocytidylic acid (PolyI:C), and cholesterol to construct subunit vaccines. We evaluated the subunit vaccine effect in C57BL/6 mice and revealed that LT33 and LT28 exhibited strong immunogenicity and induced protective efficacy against aerosol challenge with M. tuberculosis H37Rv. Notably, the combination of LT33 and LT28 led to a significant reduction of 0.77 log10 colony-forming units (CFU) of H37Rv in the lungs compared to the adjuvant control group, highlighting their potential as promising candidates for subunit vaccine against M. tuberculosis infection.

10.3389/fimmu.2024.1450124

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