Stem cell basis of a host driven transmission of antigen packed aerosols: a novel mechanism of natural vaccination for tuberculosis

Natural vaccination against pathogens is known to be achieved by herd-immunity i.e. infected human host provide immunity to the community by spreading the pathogen. Whether infected human hosts transmit vesicle packed aerosols of pathogen antigen for natural vaccination of the community has not yet been considered. We have explored a traditional healing method of aerosol-inoculation against smallpox and tuberculosis in the Sualkuchi-Hajo cultural complex of Kamarupa, an ancient Indian region known for tantra-based healing and spirituality. In the aerosol-inoculation method against TB, selected persons with TB (later identified as smear-negative TB subject) are encouraged to spread good nigudah in the community by Kirtan chanting; the good Nigudah are thought to be present within bad-nigudah or invisible krimis (tiny flesh eating living being mentioned in ancient Indian medicinal text Caraka Samhita and Atharva Veda). A 15-years of contact TB investigation study, as well as laboratory study of aerosol obtained from smear negative PTB (SN-PTB) subjects led to the identification of good Nigudah as extracellular vesicles (EVs) filled with Mtb-antigen ESAT-6. We then developed a mouse model of aerosol-inoculation using SN-PTB subject derived aerosol EVs and identified Mtb infected mesenchymal stem cells (MSCs) of the lung as the putative source of the ESAT-6+ EVs. These Mtb infected MSCs reprogram to altruistic stem cell (ASC) phenotype, which then secrete ESAT-6+ EVs to the aerosols; healthy mice receiving the aerosol develop Mtb specific herd immunity. These results expedite our ongoing work on the innate defense mechanism of ASCs against the pathogen, and provide a novel mechanism of natural vaccination, where the host extracts appropriate antigens from a pathogen, and then spread it in the community via aerosols.