A rho GDP dissociation inhibitor produced by a subset of T-regulatory cells enhances mitophagy in Mycobacterium tuberculosis infected human macrophages

• Published in: The Journal of immunology (1950) Vol. 204; no. 1_Supplement; pp. 149 - 149.24
• Main Authors: Paidipally, Padmaja, Thandi, Ramya Sivangala, Radhakrishnan, Rajesh Kumar, McAllister, Madeline K, Samten, Buka, Vankayalapati, Ramakrishna, Tripathi, Deepak
• Format: Journal Article
• Language: English
• Published: 01.05.2020
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.204.Supp.149.24

Abstract Previously, we found that a Rho GDP dissociation inhibitor (D4GDI), produced by apoptotic T regulatory cells inhibit Mycobacterium tuberculosis (Mtb) growth in human macrophages through reactive oxygen species (ROS) mediated IL-1β production. Mitochondria is an important source of ROS and critical for antibacterial properties. In the current study, we evaluated the effects of D4GDI on mitochondrial homeostasis and anti-microbial scheme during Mtb infection. Recombinant D4GDI (rD4GDI) treatment of Mtb infected human macrophages enhanced the accumulation of LC3B protein on the mitochondria and triggered mitophagy. rD4GDI treatment significantly enhanced the expression of a mitophagy receptor BCL2 and adenovirus E1B 19-kDa-interacting protein 3-like (BNIP3L). BNIP3L siRNA inhibited rD4GDI dependent accumulation of LC3B protein on the mitochondria and enhanced Mtb growth in human macrophages. Further we found that rD4GDI treatment of Mtb infected macrophages induces the expression of antimicrobial peptide phospholipase family protein phospholipase A2 group VII (PLA2G7). Further studies are underway to determine the interactions between BNIP3L, PLA2G7 and mitophagy in rD4GDI treated macrophages to inhibit Mtb growth in human macrophages.