Specific and Non-Specific Immunity in Experimental Cryptococcosis in Mice

Abstract

Host defense mechanisms often appear to be inadequate following cryptococcal invasion (1-4). Significant antibody response has not been demonstrated with any regularity in man or experimental animals during torula infection. Furthermore, cellular response in cryptococcosis is frequently sparse. The apparent inadequacy of host antibody and cellular defenses during torula infection has been related to the presence of a large capsule, surrounding the cryptococcus cell, which consists primarily of several polysaccharides (5).Benham (6) was able to produce antibodies to cryptococci in rabbits only after the capsule had been removed with hydrochloric acid. Evans and Kessel (7,8) and Neill, CastiUo, Smith, and Kapros (9), however, demonstrated precipitating and agglutinating antibodies in the rabbit following immunization with large numbers of heat-or formalin-killed cryptococci. These antibodies were dearly shown to be directed against the capsular material. The rabbit does not ordinarily develop progressive cryptococcosis so that no inference could be drawn as to the protective effect of such immunization in this animal.In recent studies, Gadebusch (10) reported that he could delay death in mice following cryptococcal challenge by the administration of immune rabbit serum. These as yet unconfirmed studies suggested that immune rabbit serum not only contained antibody directed against the cryptococcal capsule, but also was able to modify the course of a lethal cryptococeal infection. However, the challenge organisms were suspended in mucin, and the antisera and challenge were both given intraperitoneaUy within 2 hours of each other. It is quite possible that the apparent protection was related to dumping of fungi by the agglutinating antisera, thus in actuality reducing the size of the inoculum. Furthermore, mucin itself can at first reduce and later increase resistance non-specifically to many infections (11). Thus temporary dumping of fungus cells by antisera might retard the acute infection long enough to allow nonspecific resistance to develop.Gadebusch (12) also reported that death was delayed in mice infected with a lethal

The Influence of Cortisone on Experimental Fungus Infections in Mice*

“…Populations were similar in cortisone-treated and control mice 15 minutes to 24 hours after infection. Candida clearance was delayed in mice treated with cortisone.…”

“…Liver and spleen were also used for fungus enumeration in Cryptococcus experiments after it was shown that progressive infection occurred in all organs studied including liver-spleen (which were combined), lung, kidney, and brain during the first 2 weeks after infection (15). Subsequently, more detailed quantitative studies in this laboratory have demonstrated that multiplication during the first 2 weeks was somewhat less in the liverspleen than in the lungs, kidney, and brain.…”

Genomic approaches to investigate the pathogenicity of Cryptococcus neoformans

“…For example, multiple reports have documented that wildtype strains vary in animal pathogenicity [10][11][12][13] and the expression of virulence phenotypes, such as the size [ 14 ], composition [ 14 , 15 ] and biological activity of the capsule [ 16 ], production of laccase [ 17 ] and phospholipases, susceptibility to antifungal drugs, and resistance to phagocytosis and phagocytic killing mechanisms [ 12 , 18-20 ]. Many genome-wide approaches are designed to compare multiple strains and to investigate microbial populations rather than a small number of laboratory strains.…”

Immunization of Mice with a Mutant of <i>Cryptococcus neoformans</i>

“…Without entering into a detailed discussion of the various modalities used, it should suffice to enumerate the names of those who participated in these experiments. Hoff [6] v/as the trailblazer who used heat-killed cryptococci, who was followed by Kligman [7], G adebusch [4,5], Louria [8], Louria el at. [9], Louria and Kaminski [10], Marcus and Rambo [11], Abrahams and G illeran [I] and Abrahams [2], The latter combined heat-and formalin-killed cryptococci with Bordetella pertussis vaccine and achieved a survival rate of approximately 100%.…”