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Targeting innate immunity for tuberculosis vaccination
Shabaana A. Khader, … , Mihai G. Netea, on behalf of the Bill and Melinda Gates Foundation Collaboration for TB Vaccine Discovery Innate Immunity Working Group18
Shabaana A. Khader, … , Mihai G. Netea, on behalf of the Bill and Melinda Gates Foundation Collaboration for TB Vaccine Discovery Innate Immunity Working Group18
Published September 3, 2019
Citation Information: J Clin Invest. 2019;129(9):3482-3491. https://doi.org/10.1172/JCI128877.
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Targeting innate immunity for tuberculosis vaccination

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Abstract

Vaccine development against tuberculosis (TB) is based on the induction of adaptive immune responses endowed with long-term memory against mycobacterial antigens. Memory B and T cells initiate a rapid and robust immune response upon encounter with Mycobacterium tuberculosis, thus achieving long-lasting protection against infection. Recent studies have shown, however, that innate immune cell populations such as myeloid cells and NK cells also undergo functional adaptation after infection or vaccination, a de facto innate immune memory that is also termed trained immunity. Experimental and epidemiological data have shown that induction of trained immunity contributes to the beneficial heterologous effects of vaccines such as bacille Calmette-Guérin (BCG), the licensed TB vaccine. Moreover, increasing evidence argues that trained immunity also contributes to the anti-TB effects of BCG vaccination. An interaction among immunological signals, metabolic rewiring, and epigenetic reprogramming underlies the molecular mechanisms mediating trained immunity in myeloid cells and their bone marrow progenitors. Future studies are warranted to explore the untapped potential of trained immunity to develop a future generation of TB vaccines that would combine innate and adaptive immune memory induction.

Authors

Shabaana A. Khader, Maziar Divangahi, Willem Hanekom, Philip C. Hill, Markus Maeurer, Karen W. Makar, Katrin D. Mayer-Barber, Musa M. Mhlanga, Elisa Nemes, Larry S. Schlesinger, Reinout van Crevel, Raman (Krishna) Vankayalapati, Ramnik J. Xavier, Mihai G. Netea, on behalf of the Bill and Melinda Gates Foundation Collaboration for TB Vaccine Discovery Innate Immunity Working Group18

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Figure 1

Sequential activation of innate and adaptive immunity during infection, and activation of a long-term memory response through T and B lymphocytes.

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Sequential activation of innate and adaptive immunity during infection, ...
The life cycle of memory T cells is depicted in corresponding phases of pathogen infection, clearance, and memory response. In secondary lymphoid organs (e.g., lymph node [LN]), APCs process and present microbial antigen to naive T (TN) cells and convert them to effector T (Teff) cells. These Teff cells then migrate to infected peripheral tissues (e.g., lung) to control infection. After pathogen clearance, Teff cells substantially contract, but a small fraction of antigen-experienced Teff cells convert to: effector memory T (Mem Teff) cells, circulating between lymphoid organs and peripheral tissues; tissue-resident memory T (Mem TTR) cells, residing in peripheral tissues; and central memory T (Mem TC) cells, which are long-lived and reside in secondary lymphoid organs.
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