| First Author | Lee A | Year | 2024 |
| Journal | Nat Immunol | Volume | 25 |
| Issue | 1 | Pages | 41-53 |
| PubMed ID | 38036767 | Mgi Jnum | J:354803 |
| Mgi Id | MGI:7736514 | Doi | 10.1038/s41590-023-01700-0 |
| Citation | Lee A, et al. (2024) BCG vaccination stimulates integrated organ immunity by feedback of the adaptive immune response to imprint prolonged innate antiviral resistance. Nat Immunol 25(1):41-53 |
| abstractText | Bacille Calmette-Guerin (BCG) vaccination can confer nonspecific protection against heterologous pathogens. However, the underlying mechanisms remain mysterious. We show that mice vaccinated intravenously with BCG exhibited reduced weight loss and/or improved viral clearance when challenged with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 B.1.351) or PR8 influenza. Protection was first evident between 14 and 21 d post-vaccination and lasted approximately 3 months. Notably, BCG induced a biphasic innate response and robust antigen-specific type 1 helper T cell (T(H)1 cell) responses in the lungs. MyD88 signaling was essential for innate and T(H)1 cell responses, and protection against SARS-CoV-2. Depletion of CD4(+) T cells or interferon (IFN)-gamma activity before infection obliterated innate activation and protection. Single-cell and spatial transcriptomics revealed CD4-dependent expression of IFN-stimulated genes in lung myeloid and epithelial cells. Notably, BCG also induced protection against weight loss after mouse-adapted SARS-CoV-2 BA.5, SARS-CoV and SHC014 coronavirus infections. Thus, BCG elicits integrated organ immunity, where CD4(+) T cells feed back on tissue myeloid and epithelial cells to imprint prolonged and broad innate antiviral resistance. |
