LL-37 at the local site of streptococcal skin and soft-tissue infections

Background

As part of the innate immune system, antimicrobial peptides (defensins and cathelicidins) are produced by both circulating and epithelial cells. Cathelicidins have been reported as an essential component against group A streptococcal (GAS) skin infections. However, bacterial factors such as streptococcal pyrogenic exotoxin B (SpeB) may inactivate these peptides. We have studied the interaction between GAS and the human cathelicidin LL-37, by use of patient tissue material.

Methods and materials

Thirty-seven biopsies from 17 patients suffering from GAS skin and soft-tissue infection were obtained and graded according to disease severity (erysipelas, cellulitis, necrotizing fasciitis). Three additional biopsies served as negative controls. Tissue sections were immunostained for LL-37, GAS, SpeB and specific cell markers. Sections were investigated by light and confocal microscopy, and results were quantified by in situ imaging.

Results

High expression of LL-37 was detected in erysipelas and severe soft-tissue infections, and showed a significant positive correlation to bacterial load (P < 0.001 and P = 0.042, respectively). Confocal microscopy identified neutrophils as the main source of LL-37 at the epicenter of infection, and the degree of neutrophil infiltration showed a significant positive correlation to LL-37 levels (P < 0.001). LL-37 and SpeB were detected in the same biopsy areas, and colocalization was confirmed by confocal microscopy.

Conclusion

Despite the high expression of LL-37 in close proximity to streptococci at the local site of infection, there seems to be a significant lack of antimicrobial effect, as evident by the bacterial load. The colocalization of SpeB and LL-37 suggests that this streptococcal factor probably contributes significantly to a resistance mechanism towards antimicrobial peptides at the local tissue site.