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Background <p>Pulmonary commensals play a crucial role in regulating host immune homeostasis and combating infections. Nevertheless, the deep mechanisms remain unclear.</p> Results <p>Long-term antibiotics pre-exposure enhanced the susceptibility to bacterial pneumonia, while intranasal reconstitution of the pulmonary microbiota mitigated these adverse effects, restoring host resilience to infections. We isolated two pulmonary commensals, <i>Lactobacillus plantarum</i> and <i>Lactobacillus murinus</i>, demonstrating that they induced IL-17A-mediated antibacterial immunity and promoted resistance to lung infections. Moreover, antibiotics-treatment reduced the frequency of pulmonary IL-17A secreting Vγ4<sup>+</sup> γδ T cells and made the mice more susceptible to pneumonia, which was reversed by transferring pulmonary <i>Lactobacillus</i> commensals. In addition, our data indicated that <i>L</i>. <i>plantarum</i> and <i>L</i>. <i>murinus</i>-derived metabolites, particularly extracellular polysaccharides, can activate lung Vγ4<sup>+</sup> γδ T cells to secrete IL-17A in defense against bacterial lung infections.</p> Conclusions <p>In this study, we report for the first time that pulmonary commensal <i>Lactobacillus</i>, specifically <i>L</i>. <i>plantarum</i> and <i>L</i>. <i>murinus</i>, activate Vγ4<sup>+</sup> γδ T cells to secrete IL-17A, thereby mitigating susceptibility to <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> infections. Additionally, we identified the metabolite of <i>L</i>. <i>plantarum</i> and <i>L</i>. <i>murinus</i>, extracellular polysaccharides, as the key immunomodulatory molecules. This research highlights the importance of pulmonary commensals in the regulation of anti-infection immunity and provides a theoretical foundation for clinical studies on the role of lung microbiota in combating infections.</p> <p><MediaObject ID="MOESM2"> <VideoObject FileRef="MediaObjects/40168_2025_2205_MOESM2_ESM.mp4" VideoID="8G27VrxmEVcqBTJRRZmHbm"> <Caption Language="En" xml:lang="en"> <CaptionContent> <p>Video Abstract</p> </CaptionContent> </Caption> </VideoObject> </MediaObject></p>

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The pulmonary commensal Lactobacillus regulated lung γδ T cells to enhance resistance against bacterial infections

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月19日

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  • Haochi Zhang,
  • Xuemei Bao,
  • Chunhe Li,
  • Yanchen Liang,
  • Na Pan,
  • Yubing Fu,
  • Bin Ma,
  • Ting Wang,
  • Jian Chen,
  • Lipeng Zhang,
  • Xiao Wang

摘要

Background

Pulmonary commensals play a crucial role in regulating host immune homeostasis and combating infections. Nevertheless, the deep mechanisms remain unclear.

Results

Long-term antibiotics pre-exposure enhanced the susceptibility to bacterial pneumonia, while intranasal reconstitution of the pulmonary microbiota mitigated these adverse effects, restoring host resilience to infections. We isolated two pulmonary commensals, Lactobacillus plantarum and Lactobacillus murinus, demonstrating that they induced IL-17A-mediated antibacterial immunity and promoted resistance to lung infections. Moreover, antibiotics-treatment reduced the frequency of pulmonary IL-17A secreting Vγ4+ γδ T cells and made the mice more susceptible to pneumonia, which was reversed by transferring pulmonary Lactobacillus commensals. In addition, our data indicated that L. plantarum and L. murinus-derived metabolites, particularly extracellular polysaccharides, can activate lung Vγ4+ γδ T cells to secrete IL-17A in defense against bacterial lung infections.

Conclusions

In this study, we report for the first time that pulmonary commensal Lactobacillus, specifically L. plantarum and L. murinus, activate Vγ4+ γδ T cells to secrete IL-17A, thereby mitigating susceptibility to Staphylococcus aureus and Pseudomonas aeruginosa infections. Additionally, we identified the metabolite of L. plantarum and L. murinus, extracellular polysaccharides, as the key immunomodulatory molecules. This research highlights the importance of pulmonary commensals in the regulation of anti-infection immunity and provides a theoretical foundation for clinical studies on the role of lung microbiota in combating infections.

Video Abstract