BOTH INNATE AND ACQUIRED-IMMUNITY TO LISTERIA-MONOCYTOGENES INFECTIONARE INCREASED IN IL-10-DEFICIENT MICE

IL-10-deficient mice were highly resistant to Listeria monocytogenes d uring the course of infection. An increased innate immunity was sugges ted by reduced bacterial burdens (as much as 50-fold) early (days 2 an d 3) in the infection, as compared with control mice. In addition, in vitro stimulation of both IL-10-deficient peritoneal exudate cells and spleen cells with heat-killed Listeria resulted in a dramatically enh anced proinflammatory cytokine response (e.g., IL-12, IFN-gamma, TNF-a lpha IL-1 alpha, and IL-6). During later stages of a primary Listeria infection, the reduced bacterial burden in the infected organs of IL-1 0-deficient mice was accompanied by decreased tissue damage and earlie r clearance of the pathogen, as well as a stronger Th1 polarization. T he absence of IL-10 did not influence membrane-bound factors that stim ulate Th cell responses, demonstrated by the finding of normal MHC cla ss II, B7.1, and B7.2 surface expression on F4/80(+) macrophages in vi vo. IL-10-deficient mice were also more resistant to a secondary infec tion, accompanied by an enhanced Th1 response. The results presented i n this work demonstrate that the absence of IL-10 augments innate and acquired immunity during primary and secondary L. monocytogenes infect ion by up-regulating proinflammatory type 1 cytokine responses. The re sulting protective Th1 responses lead to an effective reduction of bac terial growth and tissue destruction and to an earlier clearance of th e bacteria. The physiologic role of IL-10 during L. monocytogenes infe ction studies is discussed and compared with pathogenic infections tha t induce a more systemic cytokine response in IL-10-deficient mice.