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C. Albicans Infection (c + albican_infection)
Selected AbstractsDifferential role of IL-18 and IL-12 in the host defense against disseminated Candida albicans infectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2003Mihai Abstract IFN-, plays a crucial role in the defense against infection with Candida albicans. Since IL-18 and IL-12 are strong stimuli of IFN-, production, we investigated whether endogenous IL-18 and IL-12 are involved in the host defense during disseminated candidiasis. IL-18 knockout (IL-18-/-) mice, but not IL-12-/- mice, displayed an increased mortality due to C. albicans infection, accompanied by a decreased clearance of the yeasts from the kidneys late during the course of infection. Histopathology of the organs, combined with phagocyte recruitment experiments, showed a decreased influx of monocytes at the sites of Candida infection, mainly in the IL-18-/- mice. Whereas production of the chemokine KC was decreased in both IL-18-/- and IL-12-/- mice, MIP-2 production was deficient only in IL-18-/- animals, which may explain the differences in phagocyte recruitment. In addition, although IFN-, production capacity, as a parameter of the Th1-protective immunity, was reduced by 65 to 80% in the IL-12-/- mice, this defect was even more pronounced in the IL-18-/- mice (85 to 95% downmodulation). In conclusion, the anticandidal effects of endogenous IL-18 are mediated late during the infection by assuring a proper IFN-, response and promoting the infiltration of the site of infection by monocytes. [source] Increased tumour necrosis factor-, production, higher mannose receptor activity and ability to kill Candida by concanavalin-A-activated macrophagesFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2010Thais Herrero Geraldino Abstract In a previous study, our group verified that mice pretreated with concanavalin-A (Con-A) produced more tumour necrosis factor (TNF)-, and presented greater Candida clearance from the peritoneal cavity, liver and spleen, which yielded a higher survival rate than control animals. In this work, the hypothesis that macrophages were of crucial importance in overcoming the infection was tested. Thus, peritoneal macrophages from mice pretreated for 3 days with Con-A or phosphate-buffered saline (PBS) were coincubated with CR1, CR15 and 577 isolates of Candida albicans for 0.5, 1 and 2 h. The ability of Con-activated macrophages to produce TNF-,, ingest via mannose receptors and kill all the isolates was significantly greater compared with PBS-treated macrophages, and activated macrophages exhibited a lower incidence of apoptosis, verified by binding to annexin V-fluorescein isothiocyanate. The transition of yeast cells to filamentous forms during coincubation for 2 h with control macrophages was about 73,80%, whereas in the presence of Con-A-activated macrophages, it was 35,40%. Our results suggest that a greater clearance of C. albicans infection through treatment with Con-A is probably due to the activation of macrophages, which produce more TNF-,, express more mannose receptors and are better endowed to kill ingested C. albicans. [source] Enhanced resistance against systemic Candida albicans infection in mice treated with C. albicans DNAFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2008Petya Dimitrova Abstract In this study, double-stranded Candida albicans DNA was administered in systemic C. albicans infection in at dose of 20 ,g per mouse at 4, 5 and 6 weeks of age. The level of IL-12 in serum was elevated as a result of yeast DNA treatment and correlated with lower mortality and decreased kidney and liver injury. Macrophage activation was demonstrated by an increase of nitric oxide (NO) and IL-12 production. These effects were Janus activation kinases (JAK)/signal transducer and activator of transcription (STAT) dependent as they were inhibited by selective JAK inhibitor tyrphostin AG-490. DNA influenced adaptive immune response through elevation of anti- Candida IgG antibody production in systemic C. albicans infection. Thus, C. albicans DNA augmented innate and adaptive immune responses against the pathogen. [source] Co-administration of immunomodulator tuftsin and liposomised nystatin can combat less susceptible Candida albicans infection in temporarily neutropenic miceFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2004Masood A Khan Abstract In order to develop a prospective chemotherapeutic agent against opportunistic infections, it is important to know that host factors such as degree of immunological debility as well as recovery of immune functions to normality may contribute significantly to a successful elimination of the pathogens. We demonstrated previously that concomitant delivery of antimicrobial agents and immunomodulators to the pathogen harbouring-host contributes to the complete elimination of the deep-seated fungal infections (aspergillosis and candidiasis) in animals with normal immune status. Considering that neutropenic hosts are the main targets of such infections, it can be argued about the potential of the immunomodulator-based therapy in subjects with non-functional immune system. To resolve the hypothesis, we studied the role of immunomodulator tuftsin against experimental murine candidiasis in temporarily neutropenic Balb/c mice. The neutropenic mice were challenged with an isolate of Candida albicans that was showing less susceptibility to both free and liposomised-amphotericin B. The co-administration of tuftsin increased the efficiency of liposomised-polyene antibiotics (nystatin and amphotericin B) against experimental murine candidiasis in immunocompromised Balb/c mice. Pretreatment with liposomised tuftsin prior to C. albicans infection clearly enhanced protection against candidiasis, suggesting a prophylactic role of tuftsin in normal and temporarily neutropenic animals. [source] Protection of the oral mucosa by salivary histatin-5 against Candida albicans in an ex vivo murine model of oral infectionFEMS YEAST RESEARCH, Issue 5 2010Brian M. Peters Abstract The oral cavity is a primary target for opportunistic infections, particularly oral candidiasis caused by Candida albicans. A commensal fungus commonly colonizing mucosal surfaces, under conditions of immune dysfunction, C. albicans can become a pathogen causing recurrent infections. Yet, the role of host oral innate immunity in the development of candidiasis is not fully elucidated. Specifically, the host salivary antimicrobial peptide histatin-5 (Hst-5) has been proposed to play a protective role in the oral cavity against C. albicans. However, investigations demonstrating its efficacy on oral tissue have been lacking. To this end, in this study, an ex vivo murine model of oral infection was developed. Viable C. albicans counts and histopathological analyses demonstrated a significant protective effect for Hst-5 on mouse oral tissue against C. albicans. More importantly, host saliva exerted a comparable anticandidal effect. However, this effect was neutralized upon treatment of saliva with proteases and C. albicans, previously shown to degrade Hst-5, indicating that Hst-5 is likely the salivary component responsible for the observed protection. Combined, the findings from this study demonstrate for the first time the efficacy of salivary Hst-5 in protecting host oral tissue against C. albicans infection, thereby affirming the therapeutic potential of this natural host peptide. [source] Production of hybrid phage displaying secreted aspartyl proteinase epitope of Candida albicans and its application for the diagnosis of disseminated candidiasisMYCOSES, Issue 3 2007Qiong Yang Summary The secreted aspartyl proteinases (Saps) of Candida albicans have been implicated as immunodominant antigens and virulence factors associated with adherence and tissue invasion. A hybrid phage displaying the Sap epitope VKYTS was constructed by cloning the corresponding DNA fragments into the pfd88 vector. Similar to native Sap, the phage-displayed epitope showed reactivity to sera from mice and patients with systemic C. albicans infection but not from those with oropharyngeal candidiasis and healthy individuals on Western blot. Furthermore, a new enzyme-linked immunosorbent assay was developed to detect the anti-Sap antibody with hybrid phage displaying Sap epitope VKYTS that can be recognised by anti-Sap antibodies. Sequential sera were tested from patients and mice with systemic candidiasis and oropharyngeal candidiasis, and serum samples from healthy individuals were also included. The sensitivity and specificity were 77% and 88.3% for experimental mice, respectively. These values reached 60% and 85%, respectively, for human patients. These data indicate this phage-displayed epitope as an effective and less expensive reagent would be a valuable probe for the detection of specific Sap antibody in the sera of patients and mice with systemic C. albicans infection. [source] Role of cytokines of the tumour necrosis factor family in the immune response to disseminated Candida albicans infectionBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2000M. G. Netea Background Tumour necrosis factor (TNF) ,, lymphotoxin (LT) ,, CD40L and FasL are members of the TNF family that play a crucial role in modulation of the immune response. Their role in the defence against infection with Candida albicans was investigated in mice deficient in either TNF-, and LT-, (TNF,/, LT,/, mice), CD40L (CD40L,/, mice) or Fas (MRL/lpr mice). Methods Mortality rates were compared in mice infected intravenously with 106 colony-forming units of C. albicans per mouse. Results After infection with C. albicans the TNF,/, LT,/, mice had a significantly increased mortality rate compared with control mice (100 versus 40 per cent; P < 0·01). This was due to a 10,1000-fold increased outgrowth of the yeasts in the kidneys and liver of TNF,/, LT,/, mice (P < 0·01). Defective recruitment and phagocytosis, but not Candida killing, were responsible for these effects. CD40L,/, mice were also more susceptible to systemic candidiasis than the wild-type controls (mortality rate 80 versus 50 per cent; P < 0·05), and the growth of Candida in the kidneys was one order of magnitude higher in the deficient than in control mice (P < 0·05). Neutrophil function in the CD40L,/, mice was normal, whereas decreased Candida killing by macrophages through nitric oxide-dependent mechanisms was responsible for the effect of CD40/CD40L interactions. In contrast, Fas-defective MRL/lpr mice were significantly more resistant to disseminated candidiasis (mortality rate 50 versus 100 per cent; P < 0·01); this was mediated by the facilitation of neutrophil migration to the site of infection. Conclusion Cytokines of the TNF family play a crucial role in the modulation of host defence against fatal C. albicans infection. Their effects are exerted selectively at the level of neutrophil or macrophage function. © 2000 British Journal of Surgery Society Ltd [source] | ||||||||||