bromochloroacetic-acid and Candidiasis

C. albicans triggers recurrent infections of the alimentary tract mucosa that result from biofilm growth. Although the ability of C. albicans to form a biofilm on abiotic surfaces has been well documented in recent years, no information exists on biofilms that form directly on mucosal surfaces. The objectives of this study were to characterize the structure and composition of Candida biofilms forming on the oral mucosa. We found that oral Candida biofilms consist of yeast, hyphae, and commensal bacteria, with keratin dispersed in the intercellular spaces. Neutrophils migrate through the oral mucosa and form nests within the biofilm mass. The cell wall polysaccharide beta-glucan is exposed during mucosal biofilm growth and is more uniformly present on the surface of biofilm organisms invading the oral mucosa. We conclude that C. albicans forms complex mucosal biofilms consisting of both commensal bacterial flora and host components. These discoveries are important since they can prompt a shift of focus for current research in investigating the role of Candida-bacterial interactions in the pathogenesis of mucosal infections as well as the role of beta-glucan mediated signaling in the host response.

Topics: beta-Glucans; Biofilms; Candida albicans; Candidiasis; Cell Movement; Cell Wall; Humans; Keratins; Microscopy, Confocal; Mouth Mucosa; Mucous Membrane; Neutrophils; Polysaccharides; Signal Transduction

Fungal infections have been increasing and life-threatening in recent years, but host immune responses, especially the humoral immunity, to fungi have not been fully understood. In the present study, we report that natural antibodies from unimmunized mice bind to Candida albicans. We established a monoclonal natural antibody, 3B4, which recognized a surface antigen located at germ tubes of C. albicans. The 3B4 antibody protected mice from C. albicans-induced death in passive immunization, by mechanisms involving suppressing germ tube formation and modulating phagocytosis. Interestingly, 3B4 also bound to a self-antigen keratin. To further study the generation and anti-C. albicans activities of natural antibodies in vivo, we constructed a mu chain transgenic mouse (TgV(H)3B4) using the V(H) gene from 3B4. TgV(H)3B4 had elevated serum anti-keratin/C. albicans IgM, and were resistant to C. albicans infections. Analyses of B cell development showed that in TgV(H)3B4, B cells secreting the anti-keratin/C. albicans antibodies were enriched in the B1 B cell compartment. Our findings reveal an important role of keratin-reactive natural antibodies in anti-C. albicans immune responses, and suggest that keratin may function in selecting B cells into the B1 B cell compartment, where natural antibodies are made to fight fungal infections.

Topics: Animals; Antibodies, Fungal; Candida albicans; Candidiasis; Genes, Immunoglobulin Heavy Chain; Immunity, Innate; Immunoglobulin M; Keratins; Mice; Mice, Transgenic

Rapid intraoperative examination of tissues for fungi is important for the surgical control of infection. Staining of frozen or paraffin-embedded tissues with calcofluor white (CFW) is a rapid nonspecific method for the identification of fungal infection. When viewed with a fluorescence microscope, fungal elements stained with CFW are sharply delineated from surrounding tissue and easily identified. Calcofluor white also stains tissue elements such as keratin, collagen, and elastin, which provide useful landmarks for the examination. To a much lesser degree, bacteria are also stained with CFW.

Topics: Animals; Bacterial Infections; Benzenesulfonates; Candidiasis; Collagen; Elastin; Humans; Keratins; Mice; Microscopy, Fluorescence; Mycoses; Staining and Labeling

Topics: Aspirin; Candidiasis; Cheilitis; Denture, Complete; Diagnosis, Oral; Foreign Bodies; Hyperplasia; Keratins; Leukoplakia; Lichen Planus; Palatal Neoplasms; Phenols; Salivary Duct Calculi; Stomatitis; Stomatitis, Aphthous; Stomatitis, Denture

Experimental cutaneous Candida albicans infections were produced in guinea pigs either by using occlusive dressings over the organisms or by applying them to the shaved skin directly without occlusive dressings. In either model there was clearance of the infecting organisms from the skin by a process involving profuse scaling of the keratinized layer in which they were confined. However, for each type of infection the mechanisms producing this scaling seemed to involve different parts of the host defense system. Infections produced under occlusive dressings were characterized by a rapid accumulation of polymorphonuclear leukocytes (PMN) in the epidermis and formation of thick crusts in which organisms were trapped. Sloughing of the crust removed the organisms. In this model, evolution of the lesions and the rate of clearance of the organisms did not depend on prior immunity to Candida. Two possible mechanisms for attraction of PMN into the lesions were direct activation of the alternative complement pathway by the organisms in the lesions and direct chemotactic activity in components of Candida albicans. In contrast, infections produced without occlusive dressings showed only minimal epidermal PMN infiltration, but also underwent profuse scaling of the keratinized layer. This response appeared to depend on cell-mediated immunity. Only animals with previously-acquired delayed hypersensitivity to Candida antigens could undergo this type of scaling, and indeed, this response was transferable to nonimmue animals with peritoneal exudate cells from Candida-immune animals. Clearance of the infecting organisms from this type of infection was significantly faster in immune than in nonimmune animals. It is postulated that a lymphokine released from lymphocytes in the upper epidermis acts on epidermal cells to increase the rate of keratin turnover either by the mitotic rate of the germinal cells or by increasing their rate of keratinization.

Topics: Animals; Antigens, Fungal; Ascitic Fluid; Candida albicans; Candidiasis; Chemotaxis; Complement System Proteins; Guinea Pigs; Immunity, Cellular; Immunization, Passive; Immunologic Memory; Keratins; Neutrophils; Occlusive Dressings; Skin; Skin Diseases