Differential Expression of Antimicrobial Peptides in Streptococcus pneumoniae Keratitis and STAT3-Dependent Expression of LL-37 by Streptococcus pneumoniae in Human Corneal Epithelial Cells.
Sharma. Prerana P; Sharma. Natalia N; Mishra. Priyasha P; Joseph. Joveeta J; Mishra. Dilip K DK; Garg. Prashant P; Roy. Sanhita S
Key Findings
- LL-37 is strongly induced in human corneal epithelial cells after Streptococcus pneumoniae exposure via STAT3 activation.
- LL-37 effectively kills both lab and clinical strains of Streptococcus pneumoniae in vitro.
- Other antimicrobial peptides are not induced in monocyte cells, and infection also triggers NF-ÎşB and MAPK pathways.
Practical Outcomes
- LL-37 shows promise as a topical treatment for bacterial eye infections, especially as antibiotic resistance rises. Enhancing STAT3 signaling might boost LL-37 production, but any self‑administration would require further safety and delivery research before it becomes a DIY option.
Summary
The study shows that the natural antimicrobial peptide LL-37 is produced by human eye cells when infected with the bacteria that cause eye infections, and that LL-37 can kill those bacteria. Its production depends on a cell signaling protein called STAT3, and blocking STAT3 reduces LL-37 levels.
Abstract
<i>Streptococcus pneumoniae</i> is the leading cause of bacterial keratitis in the developing world with a growing trend of acquiring resistance against various antibiotics. In the current study, we determined the expression of different antimicrobial peptides (AMPs) in response to <i>S. pneumoniae</i> in patients, as well as in primary and immortalized human corneal epithelial cells. We further focused on LL-37 and determined its expression in human cornea infected with <i>S. pneumoniae</i> and studied the killing ability of LL-37 against <i>S. pneumoniae.</i> The expression of AMPs was determined by quantitative PCR and the phosphorylation of signaling proteins was evaluated by immunoblot analysis. LL-37 expression was also determined by immunofluorescence and Western blot method and the killing ability of LL-37 against <i>S. pneumoniae</i> was determined by colony-forming units. Differential expression of antimicrobial peptides was observed in patients with <i>S. pneumoniae</i> keratitis. Although <i>S. pneumoniae</i> induced expression of the AMPs in human corneal epithelial cells (HCEC), it did not induce AMP expression in U937, a human monocyte cell line. <i>S. pneumoniae</i> also caused activation of nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB)and mitogen activated protein kinase (MAPK) pathways in corneal epithelial cells. LL-37 was found to be effective against both laboratory and clinical strains of <i>S. pneumoniae</i>. LL-37 induction by <i>S. pneumoniae</i> in human corneal epithelial cells was mediated by signal transducer and activator of transcription 3 (STAT3) activation, and inhibition of STAT3 activation significantly reduced LL-37 expression. Our study determines an extensive profile of AMPs expressed in the human cornea during <i>S. pneumoniae</i> infection, and suggests the potential of LL-37 to be developed as an alternative therapeutic intervention to fight increasing antibiotic resistance among bacteria.
Study Information
pubmed
2019
2019-03-06T00:00:00.000Z
10.3390/pathogens8010031
18
64