期刊
CELL REPORTS
卷 38, 期 1, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2021.110184
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资金
- Spanish Ministry of Economy, Industry and Competitiveness (MINECO) [BES-2014-069933]
- European Respiratory Society Fellowship [RESPIRE2-2013-3708]
- European Molecular Biology Organization Long-term Fellowship [ALTF 379-2019]
- European Union [892965]
- European Research Council (ERC) [725091]
- European Commission [635122]
- Ministerio de Ciencia e Innovacion (MICINN)
- Agencia Estatal de Investigacion (AEI)
- Fondo Europeo de Desarrollo Regional (FEDER) [SAF2016-79040-R]
- Comunidad de Madrid [B2017/BMD-3733 Immunothercan-CM]
- FIS-Instituto de Salud Carlos III
- FEDER [RD16/0015/0018-REEM]
- Inmunotek
- Fundacio La Marato de TV3 [201723]
- Fondo Solidario Juntos (Banco Santander)
- Instituto de Salud Carlos III
- MICINN
- Pro CNIC Foundation
- AEI [PID2019-108157RB]
- Atresmedia
- CNIC
- Marie Curie Actions (MSCA) [892965] Funding Source: Marie Curie Actions (MSCA)
MV130 provides protection against viral infections by inducing trained immunity. It modulates the lung immune landscape to provide long-term heterologous protection and enhances cytokine production. This study reveals the importance of inactivated bacterial vaccines in preventing respiratory infections.
MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long-term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provides protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogates the protection conferred by MV130 against influenza A virus respiratory infection. MV130 induces reprogramming of both mouse bone marrow progenitor cells and in vitro human monocytes, promoting an enhanced cytokine production that relies on a metabolic shift. Our results unveil that the mucosal administration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity.
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