Specific immune landscape of heatstroke distinguished from sepsis and aseptic inflammation

Heatstroke is associated with immune system disturbances, which was similar to sepsis and aseptic inflammation. This study characterized the immune landscape of heatstroke and compared it to sepsis or aseptic inflammation in order to identify heatstroke-specific characteristics. We prospectively recruited 40 patients with heatstroke as well as the same number of age- and sex-matched healthy controls, patients with sepsis, or cardiopulmonary bypass-induced aseptic inflammation. Blood from the four groups was collected to perform spectral flow cytometry, single-cell RNA sequencing and protein chip assay to compare the profiles of T cells, B cells, monocytes, and natural killer cells. In patients with heatstroke, the relative abundance of TLR4⁺ monocyte was significantly higher than in the other three groups, and activation of antigen presentation and inhibition of chemotaxis were observed in monocytes high expressing TLR4. Both heatstroke and sepsis were characterized by lymphopenia and T cell exhaustion, with T cell exhaustion in particular potentially associated with death and organ injury in heatstroke. The decreased cytotoxic activity of NK cells was also observed in heatstroke. In conclusion, our study described the immunological characteristics of heatstroke, which provided the theoretical basis for exploring the immunotherapy of heatstroke.