Natural Killer Cell Activity and Macrophage-Dependent Inhibition of Growth or Killing of Mycobacterium avium Complex in a Mouse Model

Abstract

Natural killer (NK) cells from spleens of normal and Mycobacterium avium complex (MAC)-infected C57 black mice (C57 BL/6 bg/+) were examined for their capacity to activate splenic and peritoneal macrophages from beige mice to inhibit or kill intracellular MAC. Peritoneal and splenic macrophages from beige mice were exposed in vitro to NK cells obtained from MAC-infected and uninfected black mice. NK cells from uninfected black mice were also treated in vitro with recombinant interleukin-2 (IL-2) for 48 h before incubation with macrophages. While control macrophages supported intracellular growth of MAC, macrophages exposed to unactivated NK cells inhibited growth of the intracellular bacteria, as determined 4 days after infection. IL-2 stimulated NK cells, and NK cells obtained from MAC-infected animals were able to activate murine macrophages in vitro to inhibit growth or kill 40.0 +/- 5% and 61.3 +/- 6% of the intracellular bacteria, respectively. In other experiments, beige mice (C57 BL/6 bg/bg) were treated intraperitoneally with NK cells obtained from MAC-infected and uninfected C57 black mice. Peritoneal macrophages harvested from beige mice treated with NK cells activated in vitro with IL-2 killed 24.4 +/- 4% of intracellular bacteria by day 4 after infection. Macrophages obtained from animals treated with NK cells harvested from MAC-infected black mice killed 58.8 +/- 7% of intracellular bacteria by 4 days after infection, in contrast with intracellular growth observed in macrophages obtained from untreated animals and from animals treated with Hanks' solution or unactivated NK cells. These crossover studies suggest that NK cells may be important in host defense against MAC.

Natural Killer (NK) Cells in Antibacterial Innate Immunity: Angels or Devils?

“…The first report on the role of NK cells during bacterial infection was related to their capacity to lyse either Shigella flexneri-infected HeLa cells (18), Legionella pneumophila-infected monocytes (19) or Mycobacterium avium-infected monocytes (20). The latter study also reported that NK cells could help macrophages to inhibit growth or kill intracellular bacilli (21). Similar findings were reported for Mycobacterium lepraemurium (22).…”

“…For example, the protective role of NK cells was demonstrated in infections induced by M. avium, M. lepraemurium or M. tuberculosis (20)(21)(22)(23)194,195). The protective role of NK cells was also demonstrated in models of infection with different strains of Salmonella (196)(197)(198).…”

Mycobacterium aviumsubsp.paratuberculosisin Veterinary Medicine

“…Phenotypically, these deficiencies make them more susceptible to pyogenic bacterial infections. Beige mice have been utilized extensively to study M. avium infections and experimental chemotherapy in AIDS patients (21,22,122). When inoculated intravenously with ca.…”

The Mycobacterium avium complex

“…In mice, resistance to early growth of M. bovis, M. lepraemurium, M. intracellulare, and M. avium may be controlled by a single dominant autosomal gene, Bcg (424). Furthermore, phagocytosis-or ligand-induced respiratory burst activity is significantly greater in macrophages from resistant animals than in macrophages from susceptible mice (372), and the transfer of immune cells (T or NK cells) from resistant to susceptible mice is associated with an increased ability of the latter animals to control M. avium infection (31). However, these observations contradict the observation that peritoneal macrophages from MAC-resistant and MAC-susceptible mice have equal capacities to ingest and inhibit or kill MAC in vitro (31).…”