Role of Triggering Receptor Expressed on Myeloid Cells-1/3 in Klebsiella-Derived Pneumosepsis

Triggering receptor expressed on myeloid cells (TREM)-1 and -2 can affect Toll-like receptor-mediated activation of immune cells. Klebsiella pneumoniae is a common cause of pneumonia-derived sepsis. Here we studied the role of TREM-1/3 and TREM-2 in the host response during Klebsiella pneumonia. Macrophages lacking either TREM-1/3 or TREM-2 were tested for their responsiveness toward K. pneumoniae and for their capacity to internalize this pathogen in vitro. TREM-1/3- and TREM-2-deficient mice were infected with K. pneumoniae via the airways, and their responses were compared with those in wild-type mice. TREM-1/3-deficient macrophages produced lower cytokine levels upon exposure to K. pneumoniae, whereas TREM-2-deficient macrophages released higher cytokine concentrations. TREM-2-deficient, but not TREM-1/3-deficient, macrophages showed a reduced capacity to phagocytose K. pneumoniae. TREM-1/3-deficient mice showed an impaired host defense during Klebsiella pneumonia, as reflected by worsened survival and increased bacterial growth and dissemination. In contrast, TREM-2 deficiency did not affect disease outcome. Although TREM-1/3 and TREM-2 influence macrophage responsiveness to K. pneumoniae in vitro, only TREM-1/3 contribute to the host response during Klebsiella pneumonia in vivo, serving a protective role.