Journal
FRONTIERS IN IMMUNOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.01202
Keywords
innate; BCG-Bacille Calmette-Guerin vaccine; macropahge; mycobacerium tuberculosis; lung
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Funding
- NIH/NIAID program Advanced Small Animal Models for the Testing of Candidate Therapeutic and Preventative Interventions against Mycobacteria at Colorado State University [HHSN272201000009I-003]
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The live attenuatedMycobacterium bovisstrain, Bacille Calmette Guerin (BCG) is a potent innate immune stimulator. In the C57BL/6 mouse model of tuberculosis, BCG vaccination leads to a significant reduction ofMycobacterium tuberculosisburden after aerogenic infection. Our studies indicated that BCG induced protection against pulmonary tuberculosis was independent of T cells and present as early as 7 days after vaccination. This protection showed longevity, as it did not wane when conventional T cell and TNF-alpha deficient mice were infected 30 days post-vaccination. As BCG induced mycobacterial killing after 7 days, this study investigated the contributions of the innate immune system after BCG vaccination to better understand mechanisms required for mycobacterial killing. Subcutaneous BCG inoculation resulted in significant CD11b(+)F4/80(+)monocyte subset recruitment into the lungs within 7 days. Further studies revealed that killing of mycobacteria was dependent on the viability of BCG, because irradiated BCG did not have the same effect. Although others have identified BCG as a facilitator of trained innate immunity, we found that BCG reduced the mycobacterial burden in the absence of mechanisms required for trained innate immunity, highlighting a role for macrophages and neutrophils for vaccine induced killing ofM. tuberculosis.
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