Human resistin protects against endotoxic shock by blocking LPS-TLR4 interaction

Area of Science:

• Immunology
• Infectious Disease
• Molecular Biology

Background:

• Helminths can modulate immune responses to protect against sepsis.
• Human resistin (hRetn) is elevated in helminth infection and sepsis, but its role is unclear.

Purpose of the Study:

• To investigate the function of hRetn in sepsis and its role in helminth-mediated protection.
• To explore hRetn's therapeutic potential in lipopolysaccharide (LPS)-induced septic shock.

Main Methods:

• Utilized hRetn-expressing transgenic mice (hRETNTg+) and recombinant hRetn.
• Employed immunoprecipitation assays, TLR4-deficient mice, and human immune cell cultures.
• Generated hRetn N-terminal peptides to block LPS function.

Main Results:

• hRetn enhanced helminth-induced protection against lethal LPS dose in mice.
• hRetn binds to Toll-like receptor 4 (TLR4) via its N-terminus.
• hRetn modulates STAT3 and TBK1 signaling, shifting responses from pro-inflammatory to anti-inflammatory.

Conclusions:

• hRetn plays a critical role in blocking LPS proinflammatory functions.
• hRetn exhibits therapeutic potential in sepsis treatment.
• hRetn is a key mediator in helminth-induced immunomodulation against sepsis.