Cell-mediated resistance to infection with Listeria monocytogenes in nude mice

Abstract

Congenitally dysthymic nude (nu/nu) NMRI mice showed increased resistance to viable Listeria monocytogenes cells during the initial phase of infection as compared with euthymic control mice. The intravenous mean lethal dose (LD50), as determined for euthymic mice after an observation time of 7 and 14 days, amounted consistently to 6 X 10(4) Listeria. The corresponding values determined in nude mice were found to be increased by either 20-fold (1.2 X 10(6) Listeria after an observation time of 7 days) or 4-fold (2.4 X 10(5) Listeria after an observation time of 14 days). The transfer of spleen cells from immune euthymic donor mice into chronically infected nude mice caused almost complete elimination of Listeria within 1 week. The injection of dextran sulfate 24 h before a secondary infection with L. monocytogenes caused loss of antibacterial resistance in both chronically infected nude mice and Listeria-immune euthymic mice, this being expressed by a rapid increase in the numbers of bacteria in the spleens as well as the occurrence of serious signs of illness.

Increased production of superoxide anion by macrophages exposed in vitro to muramyl dipeptide or lipopolysaccharide.

“…The normal response of macrophages from nude mice to priming by LPS and MDP may be a phenomenon which contributes to the surprising ability of nude (nu/nu) mice to survive a challenge infection that is lethal to normal (nu/+) littermates (38)(39)(40). Although the reason for the enhanced survival of nude mice remains unclear (40), one hypothesis is that, in the absence of T-cell-mediated immunity, nude mouse macrophages are exposed to increased amounts of bacterial products, and are thereby chronically activated.…”

Murine listeriosis as a model of antimicrobial defense

“…This interpretation is supported by the unexpected results generated by experiments that employed mice rendered deficient in selected subsets of T cells by treatment with anti-T-cell subset monoclonal antibodies. Before discussing these results, however, it needs to be remembered that a hmited role for T cells could have been predicted much earlier on the basis of results published in the 1970s (23)(24)(25) showing that athymic nude mice that are devoid of functional numbers of T cells are capable of expressing surprisingly high levels of resistance to hsteriosis. Indeed, nude mice are capable of controlhng a Listeria infection at foci of infection and of causing infection to plateau in infected organs from about day 2 of infection on.…”

“…in which a sublethal inoculum of Listeria grows log linearly without restriction to cause early death. The ability of nude mice to resist listeriosis was originally explained on the grounds that these mice have an activated macrophage system, as indicated by their ability to kill a larger proportion of the Listeria inoculum that implants in their hvers during the first few hours of infection (23)(24)(25). However, more recent studies (26) show that the explanation of this T-ceii-independent resistance is more complex, in that nude mice with a chronic primary infection acquire a capacity to completely destroy a lethal intravenous challenge inoculum of Listeria.…”

Do Natural Killer Cells Engage in Regulated Reactions Against Self to Ensure Homeostasis?

“…Both reactivities are in fact stronger in genetically athymic nu/nu mice than in euthymic nu/+OT-\-/-\-littermates. Thymus-independence.as detected in nude mice, is a common feature also for natural resistance to certain intracellular bacteria (Cheers & Waller 1975, Emmerling et al 1977, myxoviruses (Haller & Lindenman 1974) and xenogeneic cells persistently infected with a variety of viruses (Reid et al 1979). In contrast, most of these noninduced host reactivities are greatly influenced by the status of bone marrow.…”

“…Among these targets, tumor cells of different histologic types are conspicuous (Nunn et al 1977, Stutman et al 1978, Warner 1978, but tissue culture fibroblasts (Osband & Parkman 1978), virus transformed cells (Williams et al 1977, Santoli et al 1978a,b, Welsh 1978, cells persistently infected with virus (Reid et al 1979), and cells infected with Listeria monocytogenes (Bennett & Baker 1977) -even protozoa (Trischmann et al 1978, Eugui & Allison 1979 -have recently been added to the list of susceptible targets. The discovery of NK cells has revived the surveillance concept, now viewed as natural host reactivity mediated by non-T cells, especially in the light of high levels of NK cytotoxicity, resistance to infections, or resistance to the growth of transplanted ceils by congenitally athymic nude mice (Herberman et al 1975, Kiessling et al 1975a, Warner et al 1977, Stutman et al 1978, Cudkowicz 1975, Cheers & Waller 1975, Emmerling et al 1977, Haller & Lindenmann 1974, Campanile et ai. 1977, Reid et al 1979.…”