Innate immune response to Streptococcus pyogenes depends on the combined activation of TLR13 and TLR2

Area of Science:

• Immunology
• Microbiology
• Genetics

Background:

• The innate immune system's recognition of Streptococcus pyogenes, a major human pathogen, remains incompletely understood.
• Understanding pathogen recognition is crucial for developing effective treatments and vaccines.

Purpose of the Study:

• To elucidate the mechanisms of innate immune recognition of Streptococcus pyogenes in mice.
• To investigate the role of Toll-like receptors (TLRs) in S. pyogenes detection.
• To compare S. pyogenes recognition pathways in mice and humans.

Main Methods:

• Utilized mouse models deficient in Toll-like receptor 2 (TLR2) and Toll-like receptor 13 (TLR13).
• Infected macrophages and dendritic cells with S. pyogenes in vitro and in vivo.
• Analyzed inflammatory cytokine production and phagocytosis-independent/dependent recognition pathways.
• Conducted phylogenetic analysis of TLR13 distribution.

Main Results:

• Mice utilize both TLR2 and TLR13 for S. pyogenes recognition, which are non-redundant in vivo but largely redundant in vitro.
• TLR13-mediated recognition is triggered by S. pyogenes ribosomal RNA (rRNA) upon internalization.
• Human macrophages lack TLR13 and an equivalent pathway for S. pyogenes RNA recognition.
• TLR13 is present in few mammals, including mice and rats, which are naturally resistant to S. pyogenes.

Conclusions:

• Dissimilar TLR13 expression between mice and humans has functional consequences for S. pyogenes recognition.
• The absence of TLR13 in humans may contribute to differential susceptibility to S. pyogenes infection compared to mice.