Kaloula pulchra breed:frog Genome sequencing. Kaloula pulchra breed:frog

Targeted immune-enhancing therapy may be a valid method to prevent and treat sepsis, aiming to initiate or strengthen protective antimicrobial immunity while limiting inflammation-triggered tissue injury. Here, we identified the first frog-derived TLR2 and TLR4 agonist, Cath-Ka, from the skin of Kaloula pulchra. Cath-Ka administration increased the proliferation, production of cytokines and chemokines, polarization, chemotaxis, phagocytosis and intracellular bacterial killing abilities via acting on TLR2 and TLR4 rather than other pattern recognition receptors, and subsequently activating its downstream MyD88-MAPKs pathway in macrophages and mice. Notably, Prophylactic Cath-Ka treatment also significantly expedited bacterial clearance and attenuated the overproduction of inflammatory cytokines, the formation of microvascular thrombosis, and the pathological changes in septic mice through modulation of macrophage function. Altogether, these results demonstrate that Cath-Ka is an attractive candidate prophylactic treatment molecule for sepsis.