Role of NK1.1+ cells in experimental listeriosis. NK1+ cells are early IFN-gamma producers but impair resistance to Listeria monocytogenes infection.

Abstract

An enzyme-linked immunospot assay was used for detection of splenic IFN-gamma and IL-4 spot-forming cells from, C57Bl/6 and BALB/c mice, which differ in resistance to systemic L. monocytogenes infection. Numbers of spontaneous and Ag (heat-killed listeriae)-induced IFN-gamma SFC were 5- to 10-fold higher in C57Bl/6 as compared to BALB/c mice at day 1, day 7, and day 14 postinfection. In both strains of mice, Ag-induced IFN-gamma production reached maximum levels at day 7 postinfection and IL-4 production was slightly increased at day 1, decreasing thereafter. The early IFN-gamma production (day 1) in C57Bl/6 mice was abrogated by in vitro and in vivo depletion of NK1+ cells with PK136 mAbs, indicating that NK1+ cells are major IFN-gamma producers at day 1 after infection. In vivo depletion of NK1+ cells markedly increased numbers of IL-4 spot-forming cells in spleens of C57Bl/6 mice, suggesting a modulatory effect of NK1+ cells and IFN-gamma on IL-4 production. At day 5 postinfection, bacterial numbers in spleens were higher in C57Bl/6 than in BALB/c mice. Treatment with the anti-NK1.1 mAb and in vivo neutralization of IL-4 with the 11B11 mAb enhanced listerial clearing in C57Bl/6 mice. These findings suggest 1) BALB/c mice are more resistant than C57Bl/6 mice to L. monocytogenes EGD infection, 2) NK1+ cells and IL-4 play a detrimental role in L. monocytogenes infection, and 3) antilisterial resistance and levels of IFN-gamma are dissociable.