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Published in:

01-03-2016

Immunometabolism within the tuberculosis granuloma: amino acids, hypoxia, and cellular respiration

Authors: Joseph E. Qualls, Peter J. Murray

Published in: Seminars in Immunopathology | Issue 2/2016

Abstract

Tuberculosis (TB) granulomas are compact, organized agglomerations of infected and uninfected macrophages, T cells, neutrophils, and other immune cells. Within the granuloma, several unique metabolic adaptations occur to modify the behavior of immune cells, potentially favoring bacterial persistence balanced with protection against immunopathology. These include the induction of arginase-1 in macrophages to temper nitric oxide (NO) production and block T cell proliferation, inhibition of oxygen-requiring NO production in hypoxic regions, and induction of tryptophan-degrading enzymes that modify T cell proliferation and function. The spatial and time-dependent organization of granulomas further influences immunometabolism, for example through lactate production by activated macrophages, which can induce arginase-1. Although complex, the metabolic changes in and around TB granulomas can be potentially modified by host-directed therapies. While elimination of the TB bacilli is often the goal of any anti-TB therapy, host-directed approaches must also account for the possibility of immunopathologic damage to the lung.

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Title: Immunometabolism within the tuberculosis granuloma: amino acids, hypoxia, and cellular respiration
Authors: Joseph E. Qualls
Peter J. Murray
Publication date: 01-03-2016
Publisher: Springer Berlin Heidelberg
Published in: Seminars in Immunopathology / Issue 2/2016
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-015-0534-0

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