Natural killer cell inhibition of young spherules and endospores of Coccidioides immitis.

Abstract

The recent development of a method for culturing the parasitic form of Coccidioides immitis by using conditions compatible with the growth of lymphoid cells has enabled us to investigate the role of natural killer (NK) cells in defense against this pathogenic fungus. Pure cultures of spherules and endospores were grown in RPMI 1640 which contained 10% calf serum. Single cell suspensions of young spherules and endospores were incubated in the presence of freshly isolated human peripheral blood lymphocytes (PBL). After a 4-hr incubation, the colony-forming ability of the fungus was significantly reduced. Leu-11 is a monoclonal antibody that binds to the Fc receptor of NK cells. When PBL were incubated in the presence of this monoclonal antibody and complement, the colony-forming ability of C. immitis was not reduced, indicating that the effector cell involved in reduction of colony-forming units is also recognized by the Leu-11 monoclonal antibody. Classical NK activity can be enhanced by preincubation with interferon; the inhibitory activity of the PBL which are responsible for the reduction in colony-forming units of C. immitis is similarly enhanced by pretreatment with interferon. When PBL are incubated in the presence of young spherules and endospores for 24 hr, the cellfree supernatants will kill U937 target cells. In addition to stimulating the release of NK cytotoxic factor, C. immitis is susceptible to inactivation when incubated in the presence of factors released by PBL which have been incubated in the presence of either K562 or C. immitis. Other evidence reported by this laboratory demonstrates that C-reactive protein is present on the surface of NK cells and that antibody to this molecule blocks NK-mediated killing of standard tumor cell targets. Pretreatment with anti-C-reactive protein also blocks the ability of PBL to inhibit the colony-forming capacity of this fungus. These data suggest that the cell that inhibits the in vitro growth of the pathogenic fungus, C. immitis, is an NK cell.

Natural Killer Cells and Cytotoxic T Cells: Complementary Partners against Microorganisms and Cancer

“…Low numbers of NK cells are associated with increased prevalence of fungal infection, and there is a correlation between reduced NK cell cytotoxic activity and fungal infections [ 30 ]. NK cells have been shown to be active and cytotoxic against bacteria such as Salmonella typhimurium [ 31 ], Shigella flexneri [ 32 ], Mycobacterium tuberculosis [ 33 ], Staphylococcus aureus [ 34 ], Listeria monocytogenes [ 35 ], and Pseudomonas aeruginosa [ 36 ], and against mold and fungi such as Candida albicans [ 37 , 38 ], Cryptococcus neoformans [ 38 , 39 ], Aspergillus fumigatus [ 40 , 41 ], Paracoccidioides braziliensis [ 42 ], Coccidioides immitis [ 43 ], Bacillus anthracis [ 44 ], and Pneumocystis murina [ 45 ].…”

The Known and Unknown “Knowns” of Human Susceptibility to Coccidioidomycosis

“…While alveolar macrophages are present and neutrophils arrive rapidly upon spherule rupture, the role of innate lymphoid cells, NK cells, and eosinophils has not been characterized. Petkus and Baum [104] reported that NK cells are the leukocytes responsible for Coccidioides growth inhibition in vitro. This conclusion is hampered by their use of the Leu-11 antibody [104], which recognizes CD16 and is found not only on NK cells but also on neutrophils, monocytes, and macrophages.…”

“…Petkus and Baum [104] reported that NK cells are the leukocytes responsible for Coccidioides growth inhibition in vitro. This conclusion is hampered by their use of the Leu-11 antibody [104], which recognizes CD16 and is found not only on NK cells but also on neutrophils, monocytes, and macrophages. The adaptive T-cell response is critical for establishment of long-term immunity, and optimizing this has been foundational for vaccine development efforts.…”

Manipulating NK cellular therapy from cancer to invasive fungal infection: promises and challenges

“…In vitro , co-incubation setting against Coccidioides , human NK-enriched cells inhibited C. immitis endospores and spherules effectively. In this setting, interferon was used for immune augmentation and was shown to effectively enhance leucocyte-mediated fungal killing ( 101 ). As IL-2 appeared to enhance NK cell activation ( 102 ), this was added to CD16/CD56+ cell fractions against Cryptococcus with demonstrable efficacy ( 103 ).…”