Caspase-1 and -11 defend against environmental but not host-adapted pathogens in genetically complex mice

Caspase-1 and -11 deficiency provides little or no survival benefit against host-adapted Listeria monocytogenes and Salmonella Typhimurium in B6×129 F1 hybrid mice, with only a modest effect at the lowest S. Typhimurium inoculum.

• Why it matters: The work addresses why caspase-1 and -11 often show only modest protection in infection models, testing whether their evolutionary role is stronger against environmental microbes than against host-adapted pathogens.
• What they did: The authors generated B6×129 F1 hybrids that are gene-sufficient for Nramp1 and Casp11, then measured fold changes in lethal dose (ΔLD100) caused by caspase-1 and -11 deficiency for four pathogens across B6, 129, and F1 backgrounds.
• The result: Caspase-1 and -11 were required to survive environmental Burkholderia thailandensis and Chromobacterium violaceum, where deficiency lowered lethal dose by up to six orders of magnitude, supporting the environmental-defense view.

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