Trained immunity using probiotics and inactivated pathogens enhances resistance to Salmonella enterica serovar Typhimurium infection - Highlights

Sep 29, 2026

Antibiotic resistance concerns in livestock and poultry motivate alternative approaches that strengthen host defense without relying on antibiotics. This study examined how trained immunity, induced by probiotics and inactivated pathogenic bacterial strains, enhances resistance to Salmonella enterica serovar Typhimurium infection in mice and chickens. Effects were tested in TLR2-deficient mice and assessed using bacterial outer-membrane components, bacterial genome potential, and macrophage-depletion models, emphasizing the cGAS-STING pathway. Results show genome-driven, macrophage-mediated trained immunity with cGAS-STING activation and improved protection.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Objectives

Methods

Toll-like receptor 2-deficient model

Bacterial genome evaluation and macrophage depletion

Results

Conclusion

Journal of Advanced Research 79 (2026) 491–504 Contents lists available at ScienceDirect Journal of Advanced Research journal [homepage: www. elsevier. com/locate/jare](homepage: www. elsevier. com/locate/jare) | Original Manuscript | | | | --- | --- | --- | | Trained immunity using probiotics and inactivated pathogens enhances resistance to Salmonella enterica serovar Typhimurium infection by activating the cGAS-STING signal pathway in mice and chickens | | | | Junpeng Jia, Wenxin Ji, Ningna Xiong, Jian Lin ⁎, Qian Yang
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Wei gang 1, Nanjing, Jiangsu 210095, PR China | | | | h i g h l i g h t s
• Trained immunity as a potential alternative to antibiotics for enhancing disease resistance in livestock and poultry.
• Probiotics and inactivated pathogenic bacterial strains can boost host immunity, providing protection against S. Typhimurium infection.
• Role of bacterial genomes suggesting their potential as potent immunogens for broad-spectrum immune defense.
• Macrophages were identiﬁed as key players in trained immunity, with cGAS-STING pathway activation enhancing resistance to S. Typhimurium infection.
• Innovative strategies for disease prevention and control are proposed that leverage macrophage-mediated mechanisms and trained immunity. | g r a p h i c a l a b s t r a c t
| | a r t i c l e i n f o Article history: Received 11 October 2024 Revised 5 March 2025 Accepted 6 March 2025 Available online 12 March 2025 Keywords: Trained immunity S. Typhimurium Bacterial genome Macrophages cGAS-STING pathway a b s t r a c t Introduction: Concerns about antibiotic resistance have prompted interest in alternative strategies for enhancing disease resistance, particularly in livestock and poultry production. Objectives: This study explored the role of trained immunity in enhancing resistance to Salmonella enterica serovar Typhimurium (S. Typhimurium) infection in mice and chickens. Methods: We investigated the effects of probiotics and inactivated pathogenic bacterial strains on host immunity in Toll-like receptor 2-deﬁcient mice (TLR2 −/− ) to assess whether these effects were related to bacterial outer membrane components such as peptidoglycan (PNG), lipoarabinomannan (LAM) and lipoteichoic acid (LTA). Bacterial genomes were evaluated for their ability to enhance the host immune system. Macrophage-depletion models were used to identify the key immune cells involved in trained immunity, with a focus on the cGAS-STING pathway. Results: Probiotics and inactivated pathogenic strains enhanced host immunity and protected against S. Typhimurium infection. As demonstrated in the TLR2-deﬁcient mice, the effects were not dependent on bacterial outer membrane components. Instead, bacterial genomes played a signiﬁcant role in activating trained immunity. Macrophages were identiﬁed as the primary cells that mediated the ⁎ Corresponding author at: Nanjing Agricultural University, Weigang 1, Jiangsu, PR China. E-mail address: [linjian@njau.edu.cn](linjian@njau.edu.cn) (J. Lin). [https://doi.org/10.1016/j.jare.2025.03.011](https://doi.org/10.1016/j.jare.2025.03.011) 2090-1232/© 2025 The Author(s). Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)). J. Jia, W. Ji, N. Xiong et al. Journal of Advanced Research 79 (2026) 491–504 response with the cGAS-STING pathway playing a crucial role. The results observed using the mouse models led to investigating the potential application of trained immunity in poultry. Conclusion: Trained immunity activated by probiotics and inactivated bacterial pathogens enhanced resistance against S. Typhimurium infection via macrophage activation

FAQs

What strategy does the study propose to improve resistance to Salmonella Typhimurium?

It focuses on trained immunity induced by probiotics and inactivated pathogenic bacterial strains as an alternative to antibiotic-based control.

Which immune pathway is emphasized as crucial in trained immunity?

The cGAS-STING signal pathway is identified as playing a crucial role, with macrophage activation mediating the response.

How did the study test which bacterial components drive the immune effects?

It used Toll-like receptor 2-deficient mice to assess whether effects depended on outer membrane components such as peptidoglycan, lipoarabinomannan, and lipoteichoic acid, and found the effects were not dependent on these components while bacterial genomes were significant.

Sep 29, 2026

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