Butyrate Ameliorates Intraocular Bacterial Infection by Promoting Autophagy and Attenuating the Inflammatory Response
Sukhvinder Singh, Pawan Kumar Singh, Ashok Kumar
Abstract
data showed NLRP3-independent effects of butyrate. The butyrate-treated mouse retina and cells exhibited induced expression of antimicrobial molecules CRAMP (LL37) and S100A7/A8, resulting in increased bacterial phagocytosis and killing. Moreover, butyrate treatment enhanced AMP-activated protein kinase (AMPK)-dependent autophagy and promoted the co-localization of CRAMP in autophagosomes, indicating autophagy-mediated bacterial killing. Furthermore, pharmacological inhibition of autophagy in mice revealed its role in butyrate-mediated protection. Finally, butyrate exhibited synergy with antibiotic in promoting endophthalmitis resolution. Collectively, our study demonstrated the protective mechanisms of butyrate in ameliorating bacterial endophthalmitis. Therefore, butyrate derivatives could be explored as immunomodulatory and anti-bacterial therapeutics to improve visual outcomes in ocular bacterial infections.