STAT Proteins in Innate Immunity during Sepsis: Lessons from Gene Knockout Mice

The innate immune system provides immediate defense against infection and serves as the first line of host defense during infection. In innate immunity, leukocytes such as neutrophils and macrophages recognize and respond to pathogens in a non-specific manner. Therefore, the recruitment and activation of leukocytes are essential in innate immunity, and are governed by a variety of chemical mediators including cytokines. Cytokines are generally divided into 2 types, termed type-1 and type-2 cytokines. Type-1 cytokines are important in local host defense, while type-2 cytokines play a protective role when inflammatory response spreads to the body. These cytokines exert their biological functions through the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. STAT1/3/4/6 are transcription factors that mediate IFNgamma/IL-10/IL-12/IL-13 cytokine signaling, respectively. Evidence indicates that STAT proteins have a significant impact on innate immunity during sepsis. This review focuses on recent understandings in the regulation of innate immunity by STAT proteins during sepsis and septic shock. The suppressor of cytokine signaling (SOCS) proteins are a family of SH2 domain-containing cytoplasmic proteins that complete a negative feedback loop to attenuate signal transduction from cytokines that act through the JAK/STAT pathway. The participation of SOCS proteins in sepsis is also discussed.