Mechanisms of Mt.b Ag85B-Fc fusion protein against allergic asthma in mice by intranasal immunization.

Autor: Wang T; Department of Pathogenic Biology and Immunology, College of Basic Medical Science, Ningxia Medical University, Yinchuan, Ningxia, 750004, PR China., Yang Y; Clinical College of Ningxia Medical University, Yinchuan, Ningxia, 750004, PR China., Yang M; School of Geographic Science and Planning, Ningxia University, Yinchuan, Ningxia, 750021, PR China., Wang J; Department of Pathogenic Biology and Immunology, College of Basic Medical Science, Ningxia Medical University, Yinchuan, Ningxia, 750004, PR China., Hai M; Department of Pathogenic Biology and Immunology, College of Basic Medical Science, Ningxia Medical University, Yinchuan, Ningxia, 750004, PR China., Zhang W; Department of Pathogenic Biology and Immunology, College of Basic Medical Science, Ningxia Medical University, Yinchuan, Ningxia, 750004, PR China., Ma R; Department of Pathogenic Biology and Immunology, College of Basic Medical Science, Ningxia Medical University, Yinchuan, Ningxia, 750004, PR China., Ma G; Department of Pulmonary and Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750003, PR China., Wang N; Department of Pathogenic Biology and Immunology, College of Basic Medical Science, Ningxia Medical University, Yinchuan, Ningxia, 750004, PR China., Qin Y; Department of Pathogenic Biology and Immunology, College of Basic Medical Science, Ningxia Medical University, Yinchuan, Ningxia, 750004, PR China., Wang P; Ningxia Key Laboratory of Craniocerebral Diseases, School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, 750004, PR China. Electronic address: pengwang@nxmu.edu.cn., Wan Q; Department of Pathogenic Biology and Immunology, College of Basic Medical Science, Ningxia Medical University, Yinchuan, Ningxia, 750004, PR China. Electronic address: wanqiaofeng@nxmu.edu.cn.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Dec; Vol. 283 (Pt 2), pp. 137535. Date of Electronic Publication: 2024 Nov 15.
DOI: 10.1016/j.ijbiomac.2024.137535
Abstrakt: Ag85B, the primary component of the Ag85 complex and an early secreted protein by Mycobacterium tuberculosis, has shown potential for the treatment of allergic asthma (AA) when used as a Fc-fusion protein. Administered via nasal immunization, Ag85B-Fc fusion protein significantly alleviated airway inflammation and reduced the proportions of some anaphylaxis related cells in lungs, with no significant histopathological injury to major organs in ovalbumin (OVA)-induced AA model mice. To investigate the underlying immune regulatory mechanisms of Ag85B protein, integrated proteomics and transcriptomics analyses were conducted, identifying the complement and coagulation cascades, and phagosomes as the two significantly enriched pathways at both gene and protein levels. Moreover, C3ar1 (C3aR1), Itgam (CD11b), Itgb2 (CD18), fgg (FGG), Cybb (CYBB), and Ncf4 (NCF4) were identified as core target factors that play a central role in allergic and asthmatic responses. Among them, C3aR1 and CR3 consisting of CD11b and CD18, are main complement receptors, indicating that Ag85B alleviated AA by regulating C3aR1- and CR3-mediated signal transduction. The validation results were consistent with the aforementioned findings. Overall, these results provide valuable insight into the application of mucosal immunotherapy in treatment of AA, positioning Ag85B-Fc fusion protein as a safe mucosal immunotherapeutic agent for AA.
Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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