Expression and role of CD14 in mice sensitized to lipopolysaccharide by Propionibacterium acnes

Abstract

Propionibacterium acnes-primed mice develop an IFN-γ-dependent hypersensitivity towards LPS. Since CD14 plays a key role in LPS-induced cell activation the regulation and function of CD14 in this sensitization process were studied in IFN-γR-/- and the respective wild-type (wt) mice. In unprimed mice, CD14 (mRNA and protein) was either absent (liver) or only weakly expressed in organs (spleen, lung) and in plasma. Priming with P. acnes led to a moderate, mainly IFN-γ-dependent up-regulation of CD14. LPS challenge of unprimed mice induced an IFN-γ-independent increase in CD14 mRNA and CD14 protein. LPS challenge of P. acnes-primed mice induced a strong CD14 overexpression. This response was completely absent in IFN-γR-/- mice and is therefore strictly IFN-γ-dependent. The requirement for CD14 in LPS hyper-responsiveness was assessed by comparing CD14-/- and the respective wt mice with respect to their ability to produce TNF and IFN-γ, two recognized indices of LPS activity. LPS challenge without priming led to a weaker cytokine reaction in CD14-/- than in wt mice. However, priming with P. acnes enhanced the cytokine response to LPS in both wt and CD14-/- mice, although in the latter absolute levels of cytokines were lower. Therefore, hyperreactivity to LPS is characterized by an up-regulation of CD14, but the sensitization by P. acnes is not CD14 dependent.