scholarly journals Development of an Orogastrointestinal Mucosal Model of Candidiasis with Dissemination to Visceral Organs

2006 ◽  
Vol 50 (8) ◽  
pp. 2650-2657 ◽  
Author(s):  
Karl V. Clemons ◽  
Gloria M. Gonzalez ◽  
Gaurav Singh ◽  
Jackie Imai ◽  
Marife Espiritu ◽  
...  

ABSTRACT Studies were done to develop a murine model that mimics the pattern of mucosal candidiasis followed by disseminated disease seen in patients given cytotoxic chemotherapy. Developmental studies showed that suppression of mice with 5-fluorouracil beginning 3 days prior to infection and given every 7 days thereafter necessitated antibacterial treatment but resulted in a reproducible model. Candida albicans given in the drinking water resulted in oral infection by day 3 that significantly increased from days 10 to 15 and mucosal infection with 4 to 7 log10 Candida CFU in the esophagus, stomach, small intestine, and cecum. Dissemination to livers occurred and was 100% on days 5 to 15; fewer animals had kidney infection. The median kidney or liver CFU were 2 or 3 log10 CFU, respectively, on day 15; despite this, mortality was low through 21 days of infection. As a demonstration of the utility of the model to test antifungal activity, daily treatment with 10 or 50 mg/kg itraconazole significantly reduced dissemination to the liver and kidneys and reduced tongue CFU compared to controls. Overall, these studies indicate that a nonlethal model of oral and gastrointestinal mucosal candidiasis with dissemination can be established in mice. Drug efficacy in treating localized infection and in preventing or treating disseminated infection can be studied.

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Robert B. Ashman ◽  
Dipti Vijayan ◽  
Christine A. Wells

IL-12 is a cytokine with links to both innate and adaptive immunity systems. In mice, its deletion leads to acute susceptibility to oral infection with the yeastCandida albicans, whereas such mice are resistant to systemic disease. However, it is an essential component of the adaptive response that leads to the generation of Th1-type cytokine responses and protection against disseminated disease. This paper presents an overview of the role of IL-12 in models of systemic and mucosal infection and the possible relationships between them.


2010 ◽  
Vol 9 (2) ◽  
pp. 78
Author(s):  
Cane Lukisari ◽  
Dwi Setyaningtyas ◽  
Mintarsih Djamhari

Oral candidiasis is an oral mucosal infection caused by Candida albicans (CA) ornon-Candida albicans Candida (NCAC). C. tropicalis (CT) is most virulent NCACbecause it has the most adherence ability to epithelial cells in vitro as well as mediumlevel proteinase secretion. In addition, CT is the second most common colony found inhuman. Although incidence rate of oral infection was low, this species has virulencepotency, lately reported as the mayor cause of candidemia in immunocompromisedpatients. This paper reports and discusses oral candidiasis due to CT in a child whosuffered anemia with clinical sign of malnutrition. Oral nystatin suspension is therapyof choice because of patient well response, and in vitro studies reported lack ofresponse of fluconazole to candidemia due to C.tropicalis. However, nystatin oralsuspension, should be synchronized with hygiene optimalization of elimination ofpredisposition factors, and supportive therapy would provide a good prognosis.


2018 ◽  
Vol 20 (8) ◽  
Author(s):  
Juliane Meir ◽  
Elena Hartmann ◽  
Marie‐Therese Eckstein ◽  
Eva Guiducci ◽  
Florian Kirchner ◽  
...  

Author(s):  
Marija Bokor-Bratic

Oral candidiasis is an opportunistic infection caused primarily by Candida albicans. However, in recent years, species of non-albicans Candida have been implicated more frequently in mucosal infection. Candida species usually reside as commensal organisms and are part of normal oral microflora. Determining exactly how transformation from commensal to pathogen takes place and how it can be prevented is continuous challenge for clinical doctors. Candidal adherence to mucosal surfaces is considered as a critical initial step in the pathogenesis of oral candidiasis. Acrylic dentures, acting as reservoirs, play an important role in increasing the risk from Candida colonisation. Thus, this review discusses what is currently known about the adhesion of non-albicans Candida species of oral origin to buccal epithelial cells and denture acrylics.


2014 ◽  
Vol 83 (3) ◽  
pp. 958-965 ◽  
Author(s):  
Timothy J. Break ◽  
Martin Jaeger ◽  
Norma V. Solis ◽  
Scott G. Filler ◽  
Carlos A. Rodriguez ◽  
...  

Candida albicansis part of the normal commensal microbiota of mucosal surfaces in a large percentage of the human population. However, perturbations of the host's immune response or bacterial microbiota have been shown to predispose individuals to the development of opportunisticCandidainfections. It was recently discovered that a defect in the chemokine receptor CX3CR1 increases susceptibility of mice and humans to systemic candidiasis. However, whether CX3CR1 confers protection against mucosalC. albicansinfection has not been investigated. Using two different mouse models, we found that Cx3cr1 is dispensable for the induction of interleukin 17A (IL-17A), IL-22, and IL-23 in the tongue after infection, as well as for the clearance of mucosal candidiasis from the tongue or lower gastrointestinal (GI) tract colonization. Furthermore, the dysfunctional human CX3CR1 alleleCX3CR1-M280was not associated with development of recurrent vulvovaginal candidiasis (RVVC) in women. Taken together, these data indicate that CX3CR1 is not essential for protection of the host against mucosal candidiasis, underscoring the dependence on different mammalian immune factors for control of mucosal versus systemicCandidainfections.


2016 ◽  
Vol 26 (1) ◽  
pp. 1-8 ◽  
Author(s):  
M. Frenkel ◽  
M. Mandelblat ◽  
A. Alastruey-Izquierdo ◽  
S. Mendlovic ◽  
R. Semis ◽  
...  

2002 ◽  
Vol 46 (5) ◽  
pp. 1240-1245 ◽  
Author(s):  
Justina Y. Ju ◽  
Cynthia Polhamus ◽  
Kieren A. Marr ◽  
Steven M. Holland ◽  
John E. Bennett

ABSTRACT Candida glabrata is the second leading cause of adult candidemia, resulting in high mortality. Amphotericin B is considered the treatment of choice, while the efficacy of fluconazole is controversial and caspofungin efficacy is unknown. To ascertain drug efficacy in vivo, the utility of a murine model of C. glabrata infection was investigated. C. glabrata was found to cause progressive, lethal infection when injected intravenously into C57BL/6 mice with reduced oxidative microbicidal capacity due to knockout of the p47phox gene. Spleen and kidney organ CFU counts were determined in groups of mice 2 days after the mice completed 6 days of daily intraperitoneal drug treatment, which began on the day of infection. Daily injections of fluconazole at 80 mg/kg did not reduce spleen or kidney CFU counts after infection with C. glabrata strains having in vitro fluconazole MICs of 2, 32, or 256 μg/ml compared to saline-treated controls. However, this fluconazole regimen reduced spleen CFU counts in mice infected with Candida albicans, an infection that is known to be responsive to fluconazole. Caspofungin at 5 mg/kg and amphotericin B at 5 mg/kg were both effective in reducing fungal burden in spleens and kidneys of C. glabrata-infected mice. Ten mice treated for 6 days with caspofungin at 1 mg/kg survived for 15 days, though all 10 saline-injected mice died or were so ill that they had to be sacrificed by 96 h postinfection. This murine model provided evidence of the efficacy of amphotericin B and caspofungin but not of fluconazole against C. glabrata infection.


2007 ◽  
Vol 81 (15) ◽  
pp. 7902-7912 ◽  
Author(s):  
Seii Ohka ◽  
Hiroko Igarashi ◽  
Noriyo Nagata ◽  
Mai Sakai ◽  
Satoshi Koike ◽  
...  

ABSTRACT Poliovirus (PV) is easily transferred to humans orally; however, no rodent model for oral infections has been developed because of the alimentary tract's low sensitivity to the virus. Here we showed that PV is inactivated by the low pH of the gastric contents in mice. The addition of 3% NaHCO3 to the viral inoculum increased the titer of virus reaching the small intestine through the stomach after intragastric inoculation of PV. Transgenic mice (Tg) carrying the human PV receptor (hPVR/CD155) gene and lacking the alpha/beta interferon receptor (IFNAR) gene (hPVR-Tg/IfnarKO) were sensitive to the oral administration of PV with 3% NaHCO3, whereas hPVR-Tg expressing IFNAR were much less sensitive. The virus was detected in the epithelia of the small intestine and proliferated in the alimentary tract of hPVR-Tg/IfnarKO. By the ninth day after the administration of a virulent PV, the mice had died. These results suggest that IFNAR plays an important role in determining permissivity in the alimentary tract as well as the generation of virus-specific immune responses to PV via the oral route. Thus, hPVR-Tg/IfnarKO are considered to be the first oral infection model for PV, although levels of anti-PV antibodies were not elevated dramatically in serum and intestinal secretions of surviving mice when hPVR-Tg/IfnarKO were administered an attenuated PV.


Pathology ◽  
2005 ◽  
Vol 37 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Joanne M. Bowen ◽  
Rachel J. Gibson ◽  
Dorothy M. Keefe ◽  
Adrian G. Cummins

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