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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1541954
This article is part of the Research Topic Exploring Macrophage Metabolic Adaptations to Bacterial Infection: Pathways and Immune Responses View all 5 articles
Insufficient CXCL13 Secretion in leprosy Foamy Macrophages Attenuates Lymphocyte Recruitment and Antimicrobial Protein Production
Provisionally accepted
Chuan Wang 
Yuan Zhang 
Tingting Liu 
Zihao Mi 
Peidian Shi 
Zhenzhen Wang 
Wenchao Li Honglei Wang 
Hong Liu Furen Zhang *- Hospital for Skin Diseases, Shandong First Medical University, Department of Dermatology, Shandong First Medical University, Jinan, China
Background: Pathogens trigger metabolic reprogramming, leading to the formation of foamy macrophages (FMs). This process provides a favorable environment for bacterial proliferation and enables bacteria to evade immune killing.Objective: To elucidate the mechanisms by which pathogens escape immune surveillance and elimination via the formation of FMs.We constructed a FM model using monocyte-derived macrophages (MDMs) that were incubated with oxidized low-density lipoprotein (oxLDL).Subsequently, we employed bulk RNA-sequencing (bulk RNA-seq) to comprehensively analyze the immune responses in MDMs and FMs against Mycobacterium leprae (M. leprae) infection in samples from 10 healthy individuals.Results: We found that CXCL13, a component of the cytokine-cytokine receptor interaction pathway, was specifically upregulated in M. leprae infected MDMs, when compared with M. leprae infected FMs. Significantly, further functional analyses revealed that in vitro treatment with CXCL13 could enhance the expression of CXCR5, thereby promoting lymphocyte migration and secretion of antimicrobial proteins. Additionally, NLRP12 was found to be specifically and highly expressed in the NOD-like receptor signaling pathway, which was enriched in infected FMs. In macrophages, M. leprae infection increased CXCL13 expression via NF-κB signal pathway. Conversely, in FMs, mycobacteria induced upregulation of CXCL13 was suppressed by NLRP12 through the inhibition of p52 factor expression.In conclusion, the NLRP12/NF-κB/CXCL13 axis is crucial for the immune response of FMs after mycobacterial infection. These findings contribute to a deeper understanding of the pathological mechanisms of mycobacterial infection.
Keywords: Foamy macrophage, Mycobacterial infection, CXCL13, Antimicrobial proteins, NLRP12
Received: 09 Dec 2024; Accepted: 21 Mar 2025.
Copyright: © 2025 Wang, Zhang, Liu, Mi, Shi, Wang, Li, Wang, Liu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Furen Zhang, Hospital for Skin Diseases, Shandong First Medical University, Department of Dermatology, Shandong First Medical University, Jinan, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.