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Category: Clinical Microbiology; Fungi and Fungal Pathogenesis
Cryptococcus Interactions with Innate Cytotoxic Lymphocytes, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555816858/9781555815011_Chap30-1.gif /docserver/preview/fulltext/10.1128/9781555816858/9781555815011_Chap30-2.gifAbstract:
This chapter portrays the current understanding of the mechanisms involved in direct killing of Cryptococcus by innate cytotoxic lymphocytes. Binding results in natural killer (NK)- cell reorganization of the actin and microtubular cytoskeleton that is important for formation of the immunological synapse (NKIS). Syngeneic, nylon wool nonadherent, splenic cells (NK cells) were adoptively transferred into the depleted mice. The mice were injected intravenously with Cryptococcus in the presence or absence of anti-asialo GM1, which depletes NK cells. The response of NK cells to Cryptococcus has been extended to human studies. Human NK cells can be obtained from the blood, where they are present as a small percentage of the total lymphocyte population. Perforin is the effector molecule required for NK-cell killing of Cryptococcus. Via exocytosis of lytic granules, NK cells secrete effector molecules that are involved in the killing of tumor targets. NK cells can receive signals from other innate cells in response to Cryptococcus as well as produce cytokines that stimulate other effector cells and shape adaptive immune responses. Human primary NK cells also secrete gamma interferon (IFN-γ) that correlates with increased killing of Cryptococcus in vitro. Cytokines and chemokines are important mediators of immune cell function. In addition, similar to the observations of NK cells, NKT cells enhanced host defense against Cryptococcus in the presence of interleukin-12 (IL-12) and IFN-γ. Thus, similar to NK cells, cytokines are important in eliciting NKT cell responses to Cryptococcus and in direct killing of the organism.
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(A) Scanning electron micrograph of an NK-cell conjugate with C. neoformans. (B) Higher magnification of the area from panel A, showing appendages from the NK effector cell directed at the C. neoformans target. Image from Nabavi and Murphy ( 75 ). Reprinted from Infection and Immunity with permission of the publisher.
Percollfractionated splenic large granular lymphocyte (NK cell) Golgi apparatus and centrioles at the site of Cryptococcus contact. (a) Transmission electron microscopy of an NK cell conjugate with C. neoformans, identifying NK cell cytoskeletal changes. (b) Higher magnification including Golgi apparatus. Image from Hidore and associates ( 31 ). Reprinted from Infection and Immunity with permission of the publisher.
The NK cell MTOC forms near the site of contact with Cryptococcus. (A) NK cell in association with Cryptococcus as imaged by differential interference contrast imaging. (B) The same NK cell showing formation of the MTOC identified by fluorescence microscopy using antibodyspecific labeling of tubulin in association with the site of contact of Cryptococcus. Bar represents 1 μm. Images acquired by Martina Timm-McCann.
Microorganisms directly or indirectly killed by innate cytotoxic lymphocytes