|Smith, C Wayne|
Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/27/2003
Publication Date: 10/1/2003
Citation: Wu, H., Prince, J.E., Brayton, C.F., Shah, C., Zeve, D., Gregory, S.H., Smith, W.C., Ballantyne, C.M. 2003. Host resistance of cd18-knockout mice against systemic infection with listeria monocytogenes. Infection and Immunity. 71(10):5986-5993. Interpretive Summary: Published studies have shown that dietary factors (e.g., enhanced intake of fish oil) will alter the resistance to the pathogenic bacteria Listeria monocytogenes. In this paper, we investigate some additional factors that are linked to resistance to this pathogen, specifically the roll of an adhesion molecule (CD18) that is necessary for inflammation. The surprising result is that mice that fail to express CD18, survive longer than normal mice. It appears that CD18 is not necessary for host resistance to this pathogen.
Technical Abstract: Mice with targeted mutations of CD18, the common beta 2 subunit of CD11/CD18 integrins, have leukocytosis, impaired transendothelial neutrophil emigration, and reduced host defense to Streptococcus pneumoniae, a Gram-positive extracellular bacterium. Previous studies using blocking monoclonal antibodies suggested roles for CD18 and CD11b in hepatic neutrophil recruitment and host innate response to Listeria monocytogenes, a Gram-positive intracellular bacterium. We induced systemic listeriosis in CD18-knockout (ko) and wild-type (WT) mice by tail vein injection with Listeria. By 14 days postinjection (dpi), 8 of 10 WT mice died, compared with 2 of 10 CD18-ko mice (p < 0.01). Quantitative organ culture showed that numbers of Listeria in livers and spleens were similar in both groups at 20 min postinfection. By 3, 5, and 7 dpi, however, numbers of Listeria were significantly lower in livers and spleens of CD18-ko mice than in WT mice. Histopathology showed that following Listeria infection, CD18-ko mice had milder inflammatory and necrotizing lesions in both spleens and livers than did WT mice. Cytokine assay indicated that baseline interleukin-1 beta and granulyte colony-stimulating factor (G-CSF) levels were higher in CD18-ko mice than in WT, and that CD18-ko splenocytes produced higher levels of interleukin-1 beta and G-CSF than WT splenocytes under the same amount of Listeria stimulation. These findings show that CD18 is not an absolute requirement for anti-listerial innate immunity or hepatic neutrophil recruitment. We propose that the absence of CD18 in the mice results in 'priming' of innate immunity, as evidenced by elevated cytokine expression, and neutrophilic leukocytosis, which augments anti-listerial defense.