Activation of the plasma kallikrein-kinin system by Candida albicans proteinase.

An extracellular carboxyl proteinase produced by the yeast Candida albicans enhanced vascular permeability when injected into the dorsal skin of guinea pigs. The character and mechanism of the permeability-enhancing reaction were studied in vivo and in vitro. Permeability was not enhanced when the C. albicans proteinase was heat treated (100 degrees C, 5 min) or when it was treated with pepstatin, a specific carboxyl proteinase inhibitor. The permeability reaction induced by the C. albicans proteinase was not affected by pretreatment with antihistamine but was greatly augmented by simultaneous injection of a kinin potentiator, carboxypeptidase N inhibitor. However, the simultaneous injection of a kinin-degrading enzyme, carboxypeptidase B, interfered with the reaction. Furthermore, in vitro conversion of plasma prekallikrein to kallikrein by the C. albicans proteinase was observed, and the reaction was inhibited by corn trypsin inhibitor, an inhibitor of activated Hageman factor, and soybean trypsin inhibitor, a well-known inhibitor of plasma kallikrein. These results indicate that C. albicans proteinase enhances vascular permeability through activation of the plasma kallikrein-kinin system, which generates bradykinin.     

Estradiol impairs the Th17 immune response against Candida albicans

Candida albicans is a commensal opportunistic pathogen that is also a member of gastrointestinal and reproductive tract microbiota. Exogenous factors, such as oral contraceptives, hormone replacement therapy, and estradiol, may affect susceptibility to Candida infection, although the mechanisms involved in this process have not been elucidated. We used a systemic candidiasis model to investigate how estradiol confers susceptibility to infection. We report that estradiol increases mouse susceptibility to systemic candidiasis, as in vivo and ex vivo estradiol-treated DCs were less efficient at up-regulating antigen-presenting machinery, pathogen killing, migration, IL-23 production, and triggering of the Th17 immune response. Based on these results, we propose that estradiol impairs DC function, thus explaining the increased susceptibility to infection during estrus.     

Quorum-sensing system in Candida albicans]

The bacterial behavior system controlled by the cell density is described as quorum-sensing. The system is triggered via autoinducers. Various kinds of autoinducers have been identified from different bacteria. Quorum-sensing signals via autoinducers are involved in regulation of important virulences such as exotoxin, protease, and pigment production. Therefore, this system in pathogenic bacteria has a critical role in the regulation of bacterial pathogenicity. In the pathogenic fungus Candida albicans, an extracellular quorum-sensing molecule that regulates hyphal formation by this organism has been identified in recent years. Candida albicans has been shown to form biofilm on many medical devices, therefore quorum-sensing in this organism has been especially focused on from the aspect of biofilm formation.     

白色念珠菌感染免疫应答的研究进展

白色念珠菌的致病是其与机体免疫系统相互作用的结果.研究发现,白色念珠菌感染人体时,刺激机体产生固有免疫及特异性细胞免疫和体液免疫应答.其中特异性细胞免疫占主导地位.了解认识白色念珠菌感染的免疫应答对诊断、预防及治疗白色念珠菌感染具有重要意义.     

Circulating immune complexes in patients with Candida albicans infections

The existence of circulating immune complexes in patients with candidiasis has been suggested but not confirmed. In this study we have used four immune complex screening techniques (direct nephelometry, Clq binding assay, PEG-IgG assay and PEG-C4 assay) and an immune complex score compiled from results of the individual tests to establish that elevated levels of immune complexes do exist in a series of 11 patients with systemic candidiasis as compared with a group of 18 normal controls. Isolation and characterization of high molecular weight fractions from the sera of five patients with candidiasis and further purification by affinity chromatography on Sepharose 4B-protein A substantiated the presence of anti-Candida antibody and/or Candida antigen in at least three of them. The presence of complement components and IgG in these fractions further supported the existence of immune complexes containing microbial antigen and antibody.     

Innate and adaptive immunity in Candida albicans infections and saprophytism

Underlying acquired immunity to the fungus Candida albicans is usually present in adult immunocompetent individuals and is presumed to prevent mucosal colonization progressing to symptomatic infection. Exploration of immunological events leading to Candida resistance or susceptibility has indicated the central role of the innate and adaptive immune systems, the relative contribution of which may vary depending on the site of the primary infection. Nevertheless, acquired resistance to infection results from the development of Th1 responses. Cytokines produced by Thl cells activate phagocytic cells to a candidacidal state. In contrast, cytokines produced by Th2 cells inhibit Th1 development and deactivate phagocytic effector cells. Because reciprocal influences have been recognized between innate and adaptive Th immunity, it appears that an integrated immune response determines the life-long commensalism of the fungus at the mucosal level, as well as the transition from mucosal saprophyte to pathogen.     

Double positive CD4+CD8+ T cells are part of the adaptive immune response against Candida albicans

Although multiple immune cells participate in the innate and adaptive immune response against Candida albicans, the elucidation of cellular and inflammation kinetics may be a promising strategy to decipher events propitious to infection eradication. We used an in vitro Candida-human leucocyte coculture approach to study the dynamics of rare CD4+CD8+ double positive T lymphocytes (DP T) produced in response to this fungus. Our results highlight the presence of two phenotypically distinct subsets of DP T cells: CD4hiCD8lo and CD4loCD8hi, and that the different ratio of these cells correlates with infection outcome. The ratio of CD4hiCD8lo over CD4loCD8hi by day 6 was significantly higher in controlled infections and decreased when infection persisted due to a significant increase in the proportion of CD4loCD8hi. When infection was controlled, CD4hiCD8lo T cells secreted IFNγ, TNFα, IL-4 and IL-10 cytokines two days after challenge. By day 2, under conditions of persistent infection, CD4hiCD8lo and CD4loCD8hi T cells secreted significant levels of IL-4 and IL-10, respectively, compared to uninfected cultures. Frequency kinetics and original cytokine profiles detailed in this work indicate that DP T cells could participate in the adaptive immune response to C. albicans.     

Neuraminidase production by Candida albicans

A Candida albicans strain G42, isolated from a vaginal infection, was demonstrated to produce neuraminidase in culture filtrates with activity for N-acyl-neuraminic acid glycoprotein from bovine submaxillary gland, and human erythrocytes as substrates. Incubation of viable cells from G42 with human group O Rh⁺ erythrocytes released N-acetyl-neuraminic acid in a time-dependent manner. Thirty-two clinical isolates of C albicans were studied for neuraminidase production. Enzyme activity was found in culture filtrates from five strains.     

Modifications of a Candida albicans biotyping system.

Methods of preparing and plating inocula onto media for the Odds and Abbott Candida albicans biotyping system (F. C. Odds and A. B. Abbott, Sabouraudia 18:301-317, 1980; Odds and Abbott, Sabouraudia 21:79-81, 1983) were altered to utilize inexpensive and commercially available supplies and equipment. The modified system correlates well with the reference system.     

Chemotactic factor produced by Candida albicans.

Candida albicans was found to produce a substance that was chemotactically active for guinea pig polymorphonuclear neutrophils. The chemotactic factor was detected in culture filtrates of organisms grown under aeration and incubated at 37 degrees C for at least 12 h. Nutrients found to be essential for the production of chemotactic factor included glucose, yeast extract, and a mixture of amino acids. Several strains of C. albicans isolated from humans were tested, and varying degrees of chemotactic activity were found to be associated with the culture filtrates. Only one of the eight isolates did not produce a measurable amount of chemotactic activity. Culture filtrates remained chemotactically active after several cycles of freezing and thawing and after heating at 90 degrees C for 10 min. Substantial evidence is presented that the chemotactic activity is not dependent upon activation of complement.     

Th17 cells confer long-term adaptive immunity to oral mucosal Candida albicans infections

Oropharyngeal candidiasis (OPC) is an opportunistic infection caused by Candida albicans. Despite its prevalence, little is known about C. albicans-specific immunity in the oral mucosa. Vaccines against Candida generate both T helper type 1 (Th1) and Th17 responses, and considerable evidence implicates interleukin (IL)-17 in immunity to OPC. However, IL-17 is also produced by innate immune cells that are remarkably similar to Th17 cells, expressing the same markers and localizing to similar mucosal sites. To date, the relative contribution(s) of Th1, Th17, and innate IL-17-producing cells in OPC have not been clearly defined. Here, we sought to determine the nature and function of adaptive T-cell responses to OPC, using a new recall infection model. Mice subjected to infection and re-challenge with Candida mounted a robust and stable antigen-specific IL-17 response in CD4+ but not CD8+ T cells. There was little evidence for Th1 or Th1/Th17 responses. The Th17 response promoted accelerated fungal clearance, and Th17 cells could confer protection in Rag1−/− mice upon adoptive transfer. Surprisingly, CD4 deficiency did not cause OPC but was instead associated with compensatory IL-17 production by Tc17 and CD3+CD4−CD8− cells. Therefore, classic CD4+Th17 cells protect from OPC but can be compensated by other IL-17-producing cells in CD4-deficient hosts.     

Rapid identification of Candida albicans by dot-enzyme immunoassay

A highly sensitive and specific dot-enzyme immunoassay for the rapid identification of Candida albicans was developed using a murine monoclonal antibody (Mab), which adsorbed to cell surface-exposed determinants. This Mab reacted with 28 of the 28 C. albicans strains tested including the serotypes A and B and 2 C. stellatoidea. It did not react with 32 other isolates representing eight other Candida species commonly encountered in human materials. All the test could be performed in four steps in less than an hour. The yeasts were directly spotted on a strip of immunodyne membrane. Then the strip was incubated for 5 min. with the Mab, for 15 min. with a peroxidase-conjugate and for 30 min. with the enzyme substrate and 4-chloro 1 naphthol. This test proved useful for rapid and easy identification of C. albicans.     

Germination of Candida albicans induced by proline.

Blastospores of Candida albicans germinated in proline-biotin-buffer medium incubated at 37 C. Certain other amino acids in the glatamate, asparate, and pyruvate families also fostered germinaton but generally to a lesser extent than did proline. L-Cysteine, D-proline, and certain structural analogues of L-proline inhibited proline-stimualted germination. The concentration of phosphate and glucose was crucial to amino acid-stimulated germination of C. albicans. Clinical isolates and stock cultures varied in their response to the germ tube-inducing activity of proline or other amino acids. The proline-buffer medium cannot be used in a diagnostic test for production of germ tubes by isolates of yeasts.     

Allergenicity of acid protease secreted by Candida albicans

We have previously reported the cases of Candida albicans (C. alb) acid protease (CAAP)-induced atopic asthma. In this study, the allergenicity of the released enzyme CAAP was examined among asthmatic patients with positive immediate skin response to crude C. alb antigen. Among 49 patients with positive skin response to crude C. alb , anti-crude C. alb IgE antibodies were detected in 40 and anti-CAAP IgE antibodies were detected in 18. Moreover, anticrude C. alb IgE antibodies were detected in all of the patients in whom anti-CAAP IgE antibodies were detected. No correlations between IgG antibodies to both antigens or between IgE and IgG antibodies to CAAP were observed. CAAP induced significant T-cell proliferation in 20/ 28 patients showing positive T-cell proliferation response to crude C. alb antigen. Most of the patients showing positive conjunctival response to crude C. alb antigen also snowed positive response to CAAP. Most of the patients showing high levels of serum IgE antibody and positive histamine-release response of peripheral blood leukocytes to CAAP showed positive conjunctival response. The results indicate that CAAP is an important allergen in C. alb-related mucosal allergy.