Although eCIRP also stimulates other PRRs which contribute to the inflammation in sepsis, such as triggering receptor expressed on myeloid cells-1 (TREM-1) (34), the present study showed TLR4-/- Kupffer cells were barely responsive to eCIRP, indicating the predominant role of the TLR4-mediated pathway in the polarization of Kupffer cells toward the M1 phenotype. The gene discussed is TLR4; the disease is Sepsis.