Osteopontin exacerbates Pseudomonas aeruginosa-induced bacteremia in mice

Osteopontin (OPN) is a multifunctional protein involved in various pathophysiological processes. However, the role of OPN in Pseudomonas aeruginosa-related sepsis is not yet clear. Here, we found that OPN expression was elevated in plasma and spleen samples from P. aeruginosa-infected mice. To determine the function of OPN in sepsis, we used wild-type (WT) and OPN-knockout (KO) mice with P. aeruginosa-induced bacteremia. We found that OPN-KO mice exhibited reduced mortality compared with WT mice and that OPN exacerbated spleen bleeding and functional impairment. OPN-KO mice exhibited reduced secretion of pro-inflammatory cytokines, such as interferon-γ, interleukin (IL)-1β, IL-12, and tumor necrosis factor-α, whereas levels of anti-inflammatory cytokine IL-10 and the leukocyte trafficking mediator macrophage inflammatory protein (MIP)-2 were not altered. Additionally, the percentages and absolute numbers of B cells were elevated in the spleens of OPN-KO mice. Thus, OPN promoted sepsis in P. aeruginosa-infected mice and potentially blocked B cell-dependent immunity.