BCG vaccination stimulates integrated organ immunity by feedback of the adaptive immune response to imprint prolonged innate antiviral resistance.
Audrey LeeKatharine A FloydShengyang WuZhouqing FangTze Kai TanHeather M FroggattJohn M PowersSarah R LeistKendra L GullyMiranda L HubbardChunfeng LiHarold HuiDavid ScovilleAlistaire D RuggieroYan LiangAnna PavenkoVictor LujanRalph S BaricGarry P NolanPrabhu S ArunachalamMehul S SutharBali PulendranPublished in: Nature immunology (2023)
Bacille Calmette-Guérin (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 ∼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)-γ 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.
Keyphrases
- sars cov
- immune response
- single cell
- respiratory syndrome coronavirus
- dendritic cells
- weight loss
- rna seq
- toll like receptor
- regulatory t cells
- bariatric surgery
- high throughput
- high glucose
- diabetic rats
- poor prognosis
- gene expression
- drug induced
- cell therapy
- bone marrow
- coronavirus disease
- stem cells
- endothelial cells
- insulin resistance
- metabolic syndrome
- inflammatory response
- roux en y gastric bypass
- skeletal muscle
- long non coding rna
- glycemic control
- stress induced
- transcription factor
- body mass index