Abstract

During primary infection of mice by Listeria monocytogenes, bacterial elimination is dependent on the recruitment of myelomonocytic cells in the infectious foci and the activation of their bactericidal mechanisms through cytokines secreted by Listeria-specific T lymphocytes. The immune events occurring in the liver, one of the main infected organs, have not yet been studied in detail. In the present quantitative study, we describe the dynamics of recruitment of cells belonging to the lymphoid or myelomonocytic lineages in the liver. The different cell populations mobilized into the liver were isolated each day during the course of a sublethal L. monocytogenes infection and their phenotype was characterized by flow cytometry. Three distinct phases of recruitment were observed. 1) During the first day of infection, 17 x 10(6) lymphomyeloid cells were recruited in the liver with a predominance of myelomonocytic cells; 51% of the incoming cells were M1/70+; the NK cell population (detected by the 4D11 antibody) also increased transiently at this period. 2) From day 3 to 5, a high number of myelomonocytic cells infiltrated the liver (13 x 10(6) M1/70+ cells); most of these cells were macrophages (as detected with the macrophage-restricted antibody FA/11 or observed after May-Grünwald Giemsa staining); the antigranulocytic antibodies 7/4 and RB6.8C5 were found to label these mononuclear phagocytes at this period of infection. A subpopulation of Thy-1+ cells (16%) was found to be labeled by the RB6.8C5 antibody in normal liver and, at day 5 and 6, all Thy-1+ cells also bound the RB6.8C5 mAb.3) From day 5 onward, two waves of phenotypically distinct T lymphocytes were observed; the number of CD8+ T lymphocytes (15 x 10(6) cells) increased first at day 5 and peaked on day 7; CD4+ T lymphocytes (6.2 x 10(6) cells) were then recruited with a 2-day delay (on day 7) in the liver.

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