DISRUPTION OF THE CELLULAR INFLAMMATORY RESPONSE TO LISTERIA-MONOCYTOGENES INFECTION IN MICE WITH DISRUPTIONS IN TARGETED GENES

The results of this study to dissect the nature of the acquired immune response to infection with Listeria monocytogenes in mice with target ted gene disruptions show that successful resolution of disease requir es the essential presence of alpha beta T cells and the capacity to el aborate gamma interferon. In the absence of either of these entities, mice experience increasingly severe hepatitis and tissue necrosis and de within a few days. The data from this study support the hypothesis that the protective process is the efficient replacement of neutrophil s in lesions by longer-lived mononuclear phagocytes; alpha beta-T-cell -knockout mice died from progressive infection before neutrophil repla cement could occur, whereas in gamma delta-T-cell-knockout mice this r eplacement process in the liver has previously been shown to be much s lower. Ire the present study we attribute this delay to reduced produc tion of the macrophage-attracting chemokine MCP-1 in the gamma delta-T -cell-knockout animals. These data further support the hypothesis that gamma delta T cells are important in controlling the inflammatory pro cess rather than being essential to the expression of protection.