Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection


Autoři: Johannes Nemeth aff001;  Gregory S. Olson aff001;  Alissa C. Rothchild aff001;  Ana N. Jahn aff001;  Dat Mai aff001;  Fergal J. Duffy aff001;  Jared L. Delahaye aff001;  Sanjay Srivatsan aff002;  Courtney R. Plumlee aff001;  Kevin B. Urdahl aff001;  Elizabeth S. Gold aff001;  Alan Aderem aff001;  Alan H. Diercks aff001
Působiště autorů: Seattle Children’s Research Institute, Seattle, Washington, United States of America aff001;  Medical Scientist Training Program, University of Washington School of Medicine, Seattle, Washington, United States of America aff002;  Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America aff003
Vyšlo v časopise: Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection. PLoS Pathog 16(7): e1008655. doi:10.1371/journal.ppat.1008655
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008655

Souhrn

Progress in tuberculosis vaccine development is hampered by an incomplete understanding of the immune mechanisms that protect against infection with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. Although the M72/ASOE1 trial yielded encouraging results (54% efficacy in subjects with prior exposure to Mtb), a highly effective vaccine against adult tuberculosis remains elusive. We show that in a mouse model, establishment of a contained and persistent yet non-pathogenic infection with Mtb (“contained Mtb infection”, CMTB) rapidly and durably reduces tuberculosis disease burden after re-exposure through aerosol challenge. Protection is associated with elevated activation of alveolar macrophages, the first cells that respond to inhaled Mtb, and accelerated recruitment of Mtb-specific T cells to the lung parenchyma. Systems approaches, as well as ex vivo functional assays and in vivo infection experiments, demonstrate that CMTB reconfigures tissue resident alveolar macrophages via low grade interferon-γ exposure. These studies demonstrate that under certain circumstances, the continuous interaction of the immune system with Mtb is beneficial to the host by maintaining elevated innate immune responses.

Klíčová slova:

Aerosols – Alveolar macrophages – Immune response – Mouse models – Mycobacterium tuberculosis – Spleen – T cells – Tuberculosis


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