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. 2025 Apr;22(4):390-402.
doi: 10.1038/s41423-025-01267-w. Epub 2025 Feb 17.

Antigen-presenting innate lymphoid cells induced by BCG vaccination promote a respiratory antiviral immune response through the skin‒lung axis

Dou Yu  1   2 , Xintong Gao  1   2 , Fei Shao  1   2 , Zhen Liu  1   2 , Aoyi Liu  1   2 , Min Zhao  1 , Zhuozhou Tang  1   2 , Yude Guan  1   2 , Shuo Wang  3   4
Affiliations

Antigen-presenting innate lymphoid cells induced by BCG vaccination promote a respiratory antiviral immune response through the skin‒lung axis

Dou Yu et al. Cell Mol Immunol. 2025 Apr.

Abstract

The route of vaccine administration is associated with various immune outcomes, and the relationship between the route of administration and broad protection against heterologous pathogens remains unclear. Here, we found that subcutaneous vaccination with Bacillus Calmette-Guérin (BCG) promotes respiratory influenza clearance and T-cell responses. Group 1 innate lymphoid cells (ILC1s) express MHCII molecules and engage in antigen processing and presentation after BCG vaccination. During influenza virus infection, ILC1s in the lungs of BCG-vaccinated mice can present influenza virus antigens and prime Th1 cells. After subcutaneous vaccination with BCG, MHCII+ ILC1s migrate from the skin to the lungs and play an antigen-presenting role in influenza infection. Both the BCG and the BCG component lipomannan can induce MHCII expression and skin-to-lung migration of ILC1s via TLR2 signaling. Our study revealed an important regulatory mechanism by which subcutaneous vaccination with BCG promotes respiratory antiviral immune responses via the skin‒lung axis.

Keywords: Antigen-presenting innate lymphoid cells; Bacillus Calmette-Guérin; CD4+ T cells; respiratory virus infection; skin‒lung axis.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

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