How the body’s naturally secreted molecule interleukin-1 (IL-1) fights tuberculosis infection while avoiding excessive tissue damage to the host is revealed in published online this week in Nature Immunology.
IL-1 is generated in certain immune cells, such as macrophages, through the assembly of a molecular platform called the inflammasome, which contains a key component called NLRP3. Using a mouse model of tuberculosis infection, Christopher Sassetti and colleagues found that the inflammasome machinery was deactivated by the addition of nitric oxide (nitrosylation) molecules to NLRP3. The generation of anti-microbial nitric oxide species is a classic feature of the immune response to tuberculosis so this represents an in-built mechanism to limit the amount of IL-1 production in tuberculosis.
This mechanism of regulating inflammation via nitrosylation of the inflammasome could potentially be important in limiting collateral damage in persistent infections more generally.