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Biomedical Sciences ETDs
Publication Date
12-1-2009
Abstract
Autophagy is an immune effector response against a variety of intracellular pathogens, including Mycobacterium tuberculosis. Mycobacteria survive in macrophages by blocking maturation of the phagosome. Induction of autophagy by the T helper 1 (Th1) cytokine IFN-γ, or amino acid starvation, enables macrophages to overcome the phagosome maturation block and impedes mycobacterial survival. This study investigates the role of T helper 2 (Th2) cytokines Interleukin 4 (IL-4) and Interleukin 13 (IL-13) in autophagy in macrophages and their ability to eliminate intracellular mycobacteria. The Th2 cytokines abrogated autophagy and autophagy-induced transfer of mycobacteria into lysosomal compartments, thus enhancing mycobacterial survival within infected macrophages. In murine and human macrophages, inhibition of starvation-induced autophagy by IL-4 and IL-13 was dependent on Akt signaling, whereas the inhibition of IFN-γ-induced autophagy was Akt independent and signal transducer and activator of transcription 6 (STAT6) dependent. These findings establish a mechanism through which Th1-Th2 polarization differentially influences the immune control of intracellular pathogens.
Keywords
autophagy, tuberculosis, Akt, STAT6, IL-4, IL-13, macrophage, phagosome maturation, IFN (gamma)
Sponsors
PA-05-015 Research Supplement to Promote Diversity in Health-Related Research, National Institutes of Health R01 AI045148S1 Mechanism of M. tuberculosis phagosome maturation arrest.
Document Type
Dissertation
Language
English
Degree Name
Biomedical Sciences
Level of Degree
Doctoral
Department Name
Biomedical Sciences Graduate Program
First Committee Member (Chair)
Rubin, Robert
Second Committee Member
Prossnitz, Eric
Third Committee Member
Hu, Chien-An
Recommended Citation
De Haro, Sergio A.. "Immune regulation of the host autophagic response and the elimination of Mycobacterium tuberculosis." (2009). https://digitalrepository.unm.edu/biom_etds/2