Page 60 - M. Immunology

[M. Immunology-36]

PPARα Activation Leads to Antimicrobial Responses and

Inhibits Pathologic Inflammation during Mycobacterium

abscessus Infection

Cho Rong Park¹˙², Yi Sak Kim¹˙², Jin Kyung Kim¹˙², Hyeon Ji Kim¹˙², Young Jae Kim¹˙², Sang Min Jeon¹˙²,

Jin-Man Kim⁴, Eun-kyeong Jo¹˙²˙³˙*

¹Microbiology, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea, ²Medical

Science, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea, ³Infection Control
Convergence Research Center, Chungnam National University, Daejeon 35015, Republic of Korea, ⁴Pathology,
Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea

Peroxisome proliferator-activated receptor α (PPARα) is a target for host-directed therapeutics Mycobacterium
tuberculosis infection. In this study, we found that administration of gemfibrozil (GEM), a PPARα activator, reduced

the in vivo M. abscessus (Mabc) load and inflammatory response in mice. We examined the effects of PPARα agonist
GEM on Mabc infection in macrophages and in vivo. GEM showed an inhibitory effect upon the intracellular growth

of Mabc in bone marrow-derived macrophages (BMDMs) and human monocyte-derived macrophages (MDMs).
Notably, GEM of BMDMs and MDMs resulted in significant inhibition of the intracellular growth of Mabc. GEM-

mediated antimicrobial activity was mediated through PPARα, since the GEM-induced suppressive effect on
intracellular growth of Mabc in Ppara+/+ BMDMs was abrogated in Ppara-/- BMDMs. We also showed that GEM

inhibited Mabc-induced inflammatory responses in macrophages through PPARα. The inhibitory effects of GEM on
Mabc-mediated Il6 and Ilb expression in Ppara+/+ BMDMs were abrogated in Ppara-/- BMDMs. These data suggest
that GEM treatment increased the antimicrobial activity and inhibited pathologic inflammation against intracellular

Mabc through PPARα.