AUTHOR=Ganguli Geetanjali , Mukherjee Utsav , Sonawane Avinash 

TITLE=Peroxisomes and Oxidative Stress: Their Implications in the Modulation of Cellular Immunity During Mycobacterial Infection

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.01121

DOI=10.3389/fmicb.2019.01121

ISSN=1664-302X

ABSTRACT=<p>Host redox dependent physiological responses play crucial roles in the determination of mycobacterial infection process. <italic>Mtb</italic> explores oxygen rich lung microenvironments to initiate infection process, however, later on the bacilli adapt to oxygen depleted conditions and become non-replicative and unresponsive toward anti-TB drugs to enter in the latency stage. <italic>Mtb</italic> is equipped with various sensory mechanisms and a battery of pro- and anti-oxidant enzymes to protect themselves from the host oxidative stress mechanisms. After host cell invasion, mycobacteria induces the expression of NADPH oxidase 2 (NOX2) to generate superoxide radicals (<inline-formula><mml:math id="M1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msubsup><mml:mtext>O</mml:mtext><mml:mn>2</mml:mn><mml:mo>−</mml:mo></mml:msubsup></mml:mrow></mml:math></inline-formula>), which are then converted to more toxic hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) by superoxide dismutase (SOD) and subsequently reduced to water by catalase. However, the metabolic cascades and their key regulators associated with cellular redox homeostasis are poorly understood. Phagocytosed mycobacteria <italic>en route</italic> through different subcellular organelles, where the local environment generated during infection determines the outcome of disease. For a long time, mitochondria were considered as the key player in the redox regulation, however, accumulating evidences report vital role for peroxisomes in the maintenance of cellular redox equilibrium in eukaryotic cells. Deletion of peroxisome-associated peroxin genes impaired detoxification of reactive oxygen species and peroxisome turnover post-infection, thereby leading to altered synthesis of transcription factors, various cell-signaling cascades in favor of the bacilli. This review focuses on how mycobacteria would utilize host peroxisomes to alter redox balance and metabolic regulatory mechanisms to support infection process. Here, we discuss implications of peroxisome biogenesis in the modulation of host responses against mycobacterial infection.</p>