Biomedical Sciences ETDs

Publication Date



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.


autophagy, tuberculosis, Akt, STAT6, IL-4, IL-13, macrophage, phagosome maturation, IFN (gamma)


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




Degree Name

Biomedical Sciences

Level of Degree


Department Name

Biomedical Sciences Graduate Program

First Advisor

Deretic, Vojo

First Committee Member (Chair)

Rubin, Robert

Second Committee Member

Prossnitz, Eric

Third Committee Member

Hu, Chien-An