A disturbed interaction with accessory cells upon opportunistic infection with Pseudomonas aeruginosa contributes to an impaired IFN-γ production of NK cells in the lung during sepsis-induced immunosuppression

Impaired resistance to Pseudomonas aeruginosa-induced pneumonia after cecal ligation and puncture (CLP), a mouse model for human polymicrobial sepsis, is associated with decreased IFN-, but increased IL-10, levels in the lung. We investigated the so far unknown mechanisms underlying this reduced IFN- synthesis in CLP mice. CD11b(+) NK cells, but not T or NKT cells in the lung were impaired in IFN- synthesis upon challenge with Pseudomonas invitro and invivo after CLP. The inhibition of NK cells was independent of IL-10. IFN- synthesis of NK cells was only partly restored by addition of recombinant IL-12. Accessory cells including dendritic cells and alveolar macrophages were required for maximal IFN- secretion. But accessory cells of CLP mice suppressed the IFN- secretion from naive lung leukocytes. In turn, naive accessory cells were unable to restore the IFN- production from lung leukocytes of CLP mice. Thus, a disturbed interaction of accessory cells and NK cells is involved in the impaired IFN- release in response to Pseudomonas in the lung of CLP mice. Considering the importance of IFN- in the immune defense against bacteria the dysfunction of accessory cells and NK cells might contribute to the enhanced susceptibility to Pseudomonas after CLP.