Exacerbation of Murine Listeriosis by a Monoclonal

Protective immunity in mice to infection with the Gram-positive bacterium, Listeria monocytogenes, is mediated by Listeria-sensitized Tcells, but expressed by macrophages (1) . It is known (2, 3) that protective T cells are generated progressively between days 2 and 6 of a sublethal immunizing infection, and are lost progressively after this time, as active immunity is replaced by immunologic memory. However, inactivation of Listeria begins on day 2 of infection, well before active immunity peaks, and it is associated with the accumulation of monocytes at foci ofinfection in the liver and spleen (4) . It is generally assumed that blood monocytes are responsible for inactivating Listeria at foci of infection, and that inactivation is efficient only after monocytes are activated by sensitized T cells . It might be expected, therefore, that any agent that prevents monocytes from accumulating at sites of bacterial implantation would result in failure of the host to control bacterial multiplication . An agent with likely capacity to interfere with the focusing of blood monocytes at infective foci in the liver and spleen is a recently described (5) mAb specific for the type 3 complement receptor (CR3)' of murine myelomonocytic cells . This rat mAb, designated 5C6, is specific for an epitope of theCR3 molecule that is different from the epitopes seen by other anti-CR3 mAbs (5) . It profoundly inhibits the capacity ofneutrophils and monocytes to emigrate from blood into peritoneal inflammatory exudates . The purpose of this paper is to show that intravenous injection of 5C6 mAb completely prevents mice from protecting themselves against a sublethal inoculum of Listerta . It will demonstrate that the infection-promoting action of 5C6 is based on its capacity to interfere with the accumulation of monocytes at infective foci in the liver and spleen, thereby allowing the organism to multiply unrestrictedly in nonphagocytic cells .