Candida Albicans Infection In Mice Research Articles

Murine candidiasis. III. Host inflammatory responses are regulated in part by class I MHC genes.

Host responses to experimental Candida albicans infection in mice have been shown previously to be regulated by genes in the major histocompatibility complex (MHC). Results reported here show that at least part of this control can be mapped to class I MHC genes.

Protection activity induced by the bacterial vaccine, heat-killed Clostridium butyricum against Candida albicans infections in mice.

The bacterial vaccine, heat-killed Clostridium butyricum exhibits various immunomodulating activities including a strong protection activity against Candida albicans infection in mice. The analyses of immunomodulating activities induced by the vaccine showed that the vaccine stimulated macrophage and natural killer cell activity. Stimulation of delayed type hypersensitivity, IgM antibody formation and induction of γ-type interferon were observed. The vaccine was also mitogenic for B-cell lymphocytes. Among these immunomodulating activities, interferon was considered to be one of the important factors in the manifestation of in vivo anti-candida activity. Futrher studies using recombinant interferon (IFNa-A/D type interferon) confirmed the active role of interferon in the manifestation of the protection. The interferon production by the vaccine was also found to be dependent on the mouse strain used and was most active in DDY mice.

Protective effect of acidic mannan fraction of bakers' yeast on experimental candidiasis in mice.

An acidic fraction of bakers' yeast mannan, WAM025, showed a significant protective effect against Candida albicans infection in mice, but a neutral fraction of the same bakers' yeast mannan, WNM, did not exhibit this effect. Moreover, pretreatment with WAM025 resulted in a marked reduction of proliferation of C. albicans cells in the organs of the infected mice. We investigated the stimulative effect of these mannan fractions on the function of mouse peritoneal phagocytes, and found that mice administered WAM025 showed a greater increase in the number of peritoneal exudate cells, macrophages and polymorphonuclear leucocytes (PMN), than the mice treated with WNM, especially in the proportion of PMN. Peritoneal phagocytes, PMN and macrophages obtained from WAM025-treated mice showed marked candidacidal activity. Of the phagocytes, PMN were responsible for the larger part of the candidacidal activity. The myeloperoxidase activities of PMN and macrophages in WAM025-treated PEC were greater than in untreated macrophages. The myeloperoxidase activity of WAM025-treated PMN was significantly greater than that of WAM025-treated macrophages. This activity paralleled the active oxygen-releasing activity of the phagocytes. On the other hand, the phagocytic activity of phagocytes from mice administered WNM or WAM025 for C. albicans cells was identical to that of untreated phagocytes. WAM025 seems to cause enhance elimination of the pathogen from mice, by increasing the number and candidacidal activity of phagocytic cells.

Prophylaxis of Candida albicans infection with tuftsin.

The efficacy of tuftsin, a naturally-occurring immunomodulating peptide, in the prophylaxis of disseminated Candida albicans infections in mice was studied. The intravenous administration of tuftsin caused prolonged survival at all concentrations tested.

Suppression of humoral response during the course of Candida albicans infection in mice.

This paper aims at demonstrating the non-specific immunosuppression as regards thyme-dependent antigens sheep erythrocytes (SRBC) during the course of Candida albicans systemic infection. Three lots of syngeneic/BALB/c mice, 8-12 weeks of age, were used. The first normal lot was inoculated via the intraperitoneal route with a (SRBC) suspension (4 X 10(8) cells ml) in a Hank's balanced saline solution. The primary response of antibodies formed by splenic cells was measured from 4 to 8 days after inoculation using the direct plaque forming cells technique. The second lot was infected by the same route with a suspension of Candida albicans (1 X 10(7) cells). Positive retrocultures from the blood and kidneys of these infected mice were obtained. These yeasts cultivated in a Sabouraud medium were harvested after 20 h at 37 degrees C. Following the same methodology the immune response to SRBC was determined. The serum obtained from infected mice was transferred to a third lot of mice at different intervals during the course of the infection. The immune response to SRBC was done by the direct plaque-forming cells technique. Controls were carried out using normal donors and recipients. A suppression of the immune response was obtained as from the 2nd day of inoculation up to the 28th day. It was not possible to transfer such suppression passively by means of the serum. These results suggest that the systemic infection by Candida albicans induce a non-specific immunosuppression in the organism, already demonstrated in viral infections, bacteria, protozoaria and metazoaria in mammals. In some way, this will contribute to explain the mechanisms of immune response to Candida albicans.

Protective effect of muramyl dipeptide analogs against infections of Pseudomonas aeruginosa or Candida albicans in mice.

Two analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) were found to give better protection than muramyl dipeptide against intraperitoneal Pseudomonas aeruginosa infection or intravenous Candida albicans infection in mice. The analogs tested were N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine and N-acetylmuramyl-L-alpha-amino-butyryl-D-isoglutamine. The optimum treatment was 80 mg/kg per day given once daily for 4 consecutive days before infection by the intraperitoneal, intravenous, or subcutaneous route. Dose response was limited. The compounds were not orally active. Synergism was seen between N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine and gentamicin. No postinfection protection was observed. A nonspecific stimulation of macrophage cells by muramyl dipeptide analogs may contribute to the protection because antiinfective activity against Listeria monocytogenes given intraperitoneally was achieved with CBA mice.

Antifungal and antibacterial activities of diarylamidine derivatives.

The antifungal and antibacterial properties of a series of 70 diarylamidine derivatives were evaluated. Several of these compounds exhibited considerable antimicrobial potency. A survey of the structure-activity relationship demonstrated that minor structural variations resulted in significant changes of antimicrobial activity. In general, the structural features required for antifungal activity coincided with those required for antibacterial activity. Both the antifungal and the antibacterial properties of the diarylamidines depended on the presence and the positions, of both amidino groups, on the nature of the central bridge connecting the two aryl moieties, and on the nature of these aryl residues (preferably indole). The most active compound was evaluated for its activity against Candida albicans infection in mice.

Delayed lethal response to Candida albicans infection in mice bearing the Lewis lung carcinoma.

Lethality of Candida albicans was monitored in (C57BL times DBA/2)F1 mice bearing the transplanted Lewis lung carcinoma and in sham-operated controls inoculated with Hanks' balanced salt solution. The lethal response to C. albicans infection was significantly delayed in animals inoculated with the microorganism 6-16 days after transplantation of the Lewis lung carcinoma. Maximal increases in survival times were observed when C. albicans was inoculated 8-12 days following tumor transplantation. Therefore, a delay in the lethal response to C. albicans in this untreated model murine tumor system could be elicited through implantation of the Lewis lung carcinoma; preliminary studies with some other model murine tumors and with cell-free filtrates indicated that this phenomenon is not restricted to the Lewis lung carcinoma.

Effect of 5-fluorocytosine and amphotericin B on Candida albicans infection in mice.

The effects of administration of 5-fluorocytosine alone or in combination with amphotericin B on the course of fatal Candida albicans infection in mice were studied. The survival rate was 13.7% for mice treated with 5-fluorocytosine and 15.9% for mice treated with amphotericin B. When both agents were given, the rate of survival increased to 79.5%. Counts of C. albicans in the kidneys of infected mice treated with 5-fluorocytosine and amphotericin B were 100- and 10-fold less when compared with numbers in the kidneys of mice treated with either agent alone or not treated at all, respectively.

Occurrence of lymphomas and lupus erythematosus-like syndrome in the course of experimental Candida albicans infection in mice.

Occurrence of four lymphomas was seen following injection of 1.4×103Candida albicans cells to the spleen of eighty non - inbred albine mice. These neoplastic changes occurred in three to seven months of the duration of the experiment. Extensive invasion of the subcutaneous tissue by the tumor was found in one animal. Two of the animals with lymphoma also had changes in the kidneys compatible with lupus erythematosus and presence of LE cells in the blood. In other animals most frequent and extensive pathological changes were found in the kidneys and in order of frequency were as follows: thickening of the basement membrane, fibrinoid degeneration, presence of hematoxylin bodies, wireloop formation. In total, the presence of positive LE cells in blood was found in seven instances and suggestive LE cells was observed in eight animals. Finding of perisplenitis, exudative pleuritis and pericarditis gave additional support to the resemblance of observed pathological changes with human lupus erythematosus. The fact that occurrence of lymphomas and lupus erythematosus together has been reported in humans provides additional interest to the results reported.

Evaluation of reticuloendothelial system phagocytic activity during systemic Candida albicans infection in mice.

SummaryMice infected with Candida albicans exhibited enhanced RES phagocytosis as measured by the clearance of colloidal carbon from the blood stream. Production of accelerated carbon clearance required living organisms. The time of onset of acceleration seemed to be dependent upon the size of the infecting inoculum and return to normal of the clearance occurred as the infection terminated. While accelerated clearance of colloidal carbon was produced by the infection, no change was seen at any time in the rate of clearance of microaggregated human serum albumin.We thank Mr. Joseph Edelin for his expert technical assistance.

Alterations in Host Responses to Experimental Candida Albicans Infections by Bacterial Endotoxin

Abstract Some of the mechanisms responsible for endotoxin-induced resistance to experimental Candida albicans infection in mice have been investigated. Maximal protection has been demonstrated at 1 and 6 days after endotoxin and serum factors have been shown to be important in both. The enhanced resistance to candidiasis observed 1 day following endotoxin is primarily due to transferable serum factor(s). At this time, organisms are cleared from the blood stream at an increased rate. However, this effect does not appear to be due to either the presence of serum opsonins or enhanced function of the reticuloendothelial system. In animals given endotoxin 6 days previously, there is significantly less proliferation of C. albicans in the kidney, the prime target organ of this infection. Serum factors present in the blood of these animals inhibit the growth of C. albicans in vitro. Therefore, at least two, probably different, serum factors seem to be involved in endotoxin-induced resistance. These serum factors may also require as yet undefined cellular mechanisms to produce the effects that were noted.

Pathological changes in the thymus in the course of experimental chronic Candida albicans infection in mice.

Pathological changes in the thymus in the course of experimental chronic Candida albicans infection in mice.

Influence of cell-free thymus extracts on the course of experimental Candida albicans infection in mice.

Influence of cell-free thymus extracts on the course of experimental Candida albicans infection in mice.

Fungous disease as a complication of steroid therapy.

An effort is made herein to define the degree to which a dermatologist subjects his patients to the risk of fungous disease when he prescribes systemic steroid therapy. A fair amount of animal experimentation has been performed with an eye to answering this question. Much of the information deals with Candida albicans, Coccidiodes immitis, and Histoplasma capsulatum, and a less amount deals with Cryptococcus neoformans and various actinomycetes. Strangely, I could find no relevant experimental work utilizing the aspergilli, which, clinically, have been major offenders. Experimental Candida albicans infections in mice have usually been widely disseminated by the systemic administration of cortisone. 1-6 Scherr, 2 however, felt that in particularly severe Candida albicans infections cortisone actually had some ablative effect. He also believed that pituitary gonadotropic hormones lessened the tendency of the adrenocortical steroid to lower resistance to infection. Selye, 7 on the other