IL-33 regulates age-dependency of long-term immune dysfunction induced by sepsis
bioRxiv(2022)
Abstract
Sepsis survival in adults is commonly followed by immunosuppression and increased susceptibility to secondary infections. However, the long-term immune consequences of pediatric sepsis are unknown. Here, we compared the frequency of Tregs, the activation of the IL-33/ILC2s axis in M2 macrophages, and the DNA methylation of epithelial lung cells from post-septic infant and adult mice. In contrast to adults, infant mice were resistant to secondary infection and did not show impairment in tumour controls upon melanoma challenge. Mechanistically, increased IL-33 levels, Tregs expansion, and activation of ILC2s and M2-macrophages were observed in post-septic adults but not infant mice. Impaired IL-33 production in post-septic infant mice was associated with increased DNA-methylation on lung epithelial cells. Notably, IL-33 treatment boosted the expansion of Tregs and induced immunosuppression in infant mice. Clinically, adults but not pediatric post-septic patients exhibited higher counts of Tregs and sera IL-33 levels. Hence, we describe a crucial and age-dependent role for IL-33 in post-sepsis immunosuppression.
### Competing Interest Statement
The authors have declared no competing interest.
* Tregs
: Regulatory T cells
BMDM
: Bone marrow-derived macrophages
AECs
: Alveolar Epithelial Cells
GOT
: Glutamic Oxaloacetic Transaminase
ILC2s
: Type 2 innate lymphoid cells
MoreTranslated text
Key words
sepsis,immune dysfunction,age-dependency,long-term
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