Pneumocystis carinii organisms constitute a large group of heterogeneous atypical microscopic fungi that are able to infect immunocompromised mammals by an airborne route and to proliferate in their lungs, inducing Pneumocystis carinii pneumonia. This pneumonia remains a crucial epidemiological challenge, since neither the source of Pneumocystis carinii infection in humans nor the process by which humans become infected has been clearly established. Polymerase chain reaction (PCR) assays have shown that profoundly immunosuppressed patients without pneumocystosis can be subclinically infected with Pneumocystis. Other PCR-based studies have suggested that healthy immunocompetent hosts are not latent carriers of the parasite. However, recent reports have indicated that Pneumocystis carinii can persist for limited periods in the lungs of convalescent rats after recovery from corticosteroid-induced pneumocystosis, and also that immunocompetent mammals can be transiently parasitized by Pneumocystis carinii after close contact with hosts with Pneumocystis carinii pneumonia. Can transiently parasitized hosts be a source of infection for immunosuppressed hosts? In order to investigate this important clinical question, the ability of immunocompetent BALB/c mice, which were carrying subclinical levels of Pneumocystis carinii, to transmit the infection by the airborne route to highly susceptible, uninfected mice with severe combined immunodeficiency was studied. The results indicated that the immunocompetent mice, transiently parasitized by Pneumocystis carinii organisms after close contact with Pneumocystis carinii-infected mice, were able to transmit the infection to Pneumocystis carinii-free mice with severe combined immunodeficiency.
Rat monoclonal yeast killer toxin (KT)-like immunoglobulin M (IgM) anti-idiotypic antibodies (KT-IdAbs) were produced by idiotypic vaccination with a mouse monoclonal antibody (MAb; MAb KT4) that neutralized a Pichia anomala KT characterized by a wide spectrum of antimicrobial activity. The characteristics of the KT-IdAbs were demonstrated by their capacity to compete with the KT to the idiotype of MAb KT4 and to interact with putative KT cell wall receptors (KTRs) of sensitive Candida albicans cells. The internal-image properties of KT-IdAbs were proven by their killer activity against KT-sensitive yeasts. This lethal effect was abolished by prior adsorption of KT-IdAbs with MAb KT4. These findings stressed the potential importance of antibody-mediated immunoprotection against candidiasis and suggested a feasible experimental approach for producing antimicrobial receptor antibodies without purifying the receptor. KT-IdAbs might represent the basis for producing engineered derivatives with a high potential for effective therapeutic antifungal activity. MATERIALS AND METHODS Strains. P. anomala ATCC 96603 (formerly defined as UP 25F) was used for KT production. P. anomala UM3 and C. albicans UP 10, two yeast isolates known to be sensitive to the activity of the P. anomala KT, were also used in this study. These yeasts were subcultured on Sabouraud dextrose agar plates (Difco Laboratories, Detroit, Mich.) and are maintained in sterile distilled water in our fungus collection. KT production. KT was produced by a previously described procedure (21). Briefly, P. anomala ATCC 96603 was grown for 24 h at 25ЊC in Sabouraud broth (Difco) buffered at pH 4.6 with 0.1 M citric acid and 0.2 M sodium phosphate. The supernatant was filtered and concentrated 50 times with Minicon B15 concentrators (Amicon Division, W. R. Grace & Co., Beverly, Mass.). The concentrated KT was tested for killer activity against a recognized sensitive strain by conventional well assay (33) and was refrigerated (4ЊC) until it was used. Animals. Fischer-344 rats (CPA Rot, Roquemaure, France) were used in this study to produce KT-IdAbs. Immunogen. An immunoglobulin G1 (IgG1) MAb (MAb KT4) which neutralized the activity of P. anomala KT against recognized KT-sensitive strains of C. albicans and which was produced by standard procedures as described previ
The results strongly suggest that human KTAb, elicited by a common transphyletic receptor of different pathogenic microorganisms during infection, may play a role in antibody-mediated cross-immunity and, if properly engineered, as functionally equivalent recombinant antibodies they could exert a therapeutic activity against pneumocystosis in vivo.
A Pichia anomala killer toxin has been demonstrated to have a specific inhibitory effect on the in vitro attachment of Pneumocystis carinii. The results presented herein show that this yeast toxin is also effective against P. carinii infectivity in reducing parasite colonization in the lungs of SCID mice. The specificity of this inhibitory effect was controlled using a monoclonal antibody neutralizing the killer properties of the yeast toxin.
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