Role of interleukin 1 receptor like 1 (ST2) in gram-negative and gram-positive sepsis in mice

Interleukin 1 receptor-like 1 (ST2) has been implicated as a negative regulator of Toll-like receptor signaling. We here sought to elucidate the role of ST2 in cytokine release and systemic infection caused by two common human sepsis pathogens, Streptococcus pneumoniae (gram-positive) and Klebsiella pneumoniae (gram-negative). Whole blood leukocytes and splenocytes were harvested from ST2-deficient (st2) and wild-type (WT) mice and stimulated ex vivo with S. pneumoniae or K. pneumoniae. In addition, st2 and WT mice were infected intravenously with these bacteria, and bacterial loads and cytokine levels were measured in blood, spleens and lungs at 6, 24, and 48 h thereafter. Unexpectedly, st2 blood leukocytes and splenocytes produced lower levels of cytokines and chemokines than WT cells in response to either pathogen. In contrast, the in vivo role of ST2 during sepsis caused by these bacteria was limited, although at 6 and 24 h after infection with S. pneumoniae bacterial loads were lower in spleens of st2 mice. ST2 augments rather than inhibits cytokine release by blood leukocytes and splenocytes exposed to S. pneumoniae or K. pneumoniae, but plays a limited role in host defense during sepsis caused by these pathogens