ORIGINAL RESEARCH article
Front. Immunol.
Sec. Systems Immunology
This article is part of the Research TopicTuberculosis and Immune RegulationView all 5 articles
Immunomodulation by Bacterial Products Promotes Innate Signatures Favorable to Macrophage Responses in Tuberculosis Infection
Provisionally accepted
Dámaris Priscila Romero Rodríguez1
Eduardo Montes Martínez2Héctor Isaac Rocha González3
Martha Torres Rojas4
Joaquín Zúñiga5
Esmeralda Juárez6*- 1Laboratorio Nacional Conahcyt de Investigación y Diagnóstico por Inmunocitofluorometría (LANCIDI), Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
- 2Laboratorio de Biología Molecular, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
- 3Escuela Superior de Medicina, Instituto Politecnico Nacional, Mexico City, Mexico
- 4Subdirección de Investigación Biomédica, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
- 5Laboratorio de Inmunología y Genética, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
- 6Laboratorio de Alta Contención Biológica (LACBio), Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
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Tuberculosis remains a leading cause of death from infectious diseases globally, underscoring the need to boost innate responses in monocytes and macrophages to enhance early control of Mycobacterium tuberculosis infection. Trained immunity, a form of innate immune memory, enhances macrophage responsiveness through epigenetic and metabolic reprogramming, offering a promising approach to strengthen host defenses against M. tuberculosis. This study evaluated the immunomodulatory potential of pharmaceutical-grade bacterial suspension (BS) and bacterial lysates (BL) in human monocyte-derived macrophages (MDM) and their role in innate response to M. tuberculosis infection. MDMs were stimulated with M. bovis BCG, BS, and BL following a training protocol described for BCG-dependent trained immunity. We observed that BS and BL induced sustained cytokine responses and a metabolic transcriptional profile upon secondary stimulation with M. tuberculosis. BS and BL promoted increased IL-1β production in M. tuberculosis-infected MDMs. Additionally, the expression of surface markers shifted to high levels of CD80, CD86, HLA-DR, TLR2, and CD16 and low expression of CD163, TLR9, CCR2, and TLR4, consistent with an M1 phenotype. Moreover, BS and BL upregulated antimicrobial transcriptional signatures, including autophagy-related MAP1LC3 and ATG16L1. These findings indicate that BS and BL engage training-associated transcriptional and phenotypic changes, providing new adjunctive strategies to boost innate responses in tuberculosis and other chronic infections.
Keywords: Bacterial lysates, Bacterial suspension, Macrophages, metabolic immunomodulation, trained immunity, Tuberculosis
Received: 11 Jul 2025; Accepted: 04 Dec 2025.
Copyright: © 2025 Romero Rodríguez, Montes Martínez, Rocha González, Rojas, Zúñiga and Juárez. 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: Esmeralda Juárez
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