Research reveals immune responses initiated by host-derived signals in macrophages, suggesting targeting inflammation may prevent excessive immune reactions.
Description Macrophages detect invading microorganisms through pattern recognition receptors that recognize pathogen-associated molecular patterns or by sensing microbial activities. Tissue stress following pathogen encounters results in the release of host-derived factors that contribute to inflammation. The mechanisms by which these self-derived molecules are sensed by macrophages and their impact on immunity were not fully understood. Our research demonstrated that in both mice and humans, host-derived oxidized phospholipids (oxPLs) were generated upon microbial encounter. Blocking oxPLs limited inflammation and prevented host death without affecting pathogen load. Mechanistically, oxPLs bound and inhibited AKT, a central regulator of immunity and metabolism. AKT inhibition enhanced the methionine cycle and epigenetically suppressed Il10, a key anti-inflammatory cytokine. These findings revealed that host-derived inflammatory signals can drive immune responses, and targeting their activity may protect the host from excessive inflammation during microbial encounters. Funding Sources M.D.G. is supported by the Crohn’s and Colitis Foundation, award number 854391.
No takes yet. Share an insight, caveat, or question.
Gioia et al. (2025) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: