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Int. J. Mol. Sci. 2014, 15(8), 14848-14867; doi:10.3390/ijms150814848

Multi-Step Pathogenesis and Induction of Local Immune Response by Systemic Candida Albicans Infection in an Intravenous Challenge Mouse Model

1
Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia
2
Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia
3
Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia
4
Translational Infectious Diseases Program, Centre for Translational Medicine, Department of Microbiology, National University of Singapore, Level 15 MD6, 5 Science Drive 2, National University of Singapore, Singapore 117597, Singapore
*
Authors to whom correspondence should be addressed.
Received: 12 June 2014 / Revised: 11 July 2014 / Accepted: 25 July 2014 / Published: 22 August 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Different murine species differ in their susceptibility to systemic infection with Candida albicans, giving rise to varied host immune responses, and this is compounded by variations in virulence of the different yeast strains used. Hence, this study was aimed at elucidating the pathogenesis of a clinical C. albicans isolate (HVS6360) in a murine intravenous challenge model by examining the different parameters which included the counts of red blood cells and associated components as well as the organ-specific expression profiles of cytokines and chemokines. Kidneys and brains of infected mice have higher fungal recovery rates as compared to other organs and there were extensive yeast infiltration with moderate to severe inflammation seen in kidney and brain tissues. Red blood cells (RBCs) and haemoglobin (Hb) counts were reduced throughout the infection period. Pattern recognition receptors (PRRs), chemokines and cytokine transcription profiles were varied among the different organs (kidney, spleen and brain) over 72 h post infections. Transcription of most of the PRRs, cytokines and chemokines were suppressed at 72 h post infection in spleen while continuous expression of PRRs, cytokines and chemokines genes were seen in brain and kidney. Reduction in red blood cells and haemoglobin counts might be associated with the action of extracellular haemolysin enzyme and haeme oxygenase of C. albicans in conjunction with iron scavenging for the fungal growth. Renal cells responsible for erythropoietin production may be injured by the infection and hence the combined effect of haemolysis plus lack of erythropoietin-induced RBC replenishment leads to aggravated reduction in RBC numbers. The varied local host immune profiles among target organs during systemic C. albicans infection could be of importance for future work in designing targeted immunotherapy through immunomodulatory approaches. View Full-Text
Keywords: Candida albicans; erythropoietin (EPO); pattern recognition receptors (PRRs); cytokines; chemokines; red blood cells and haemoglobin Candida albicans; erythropoietin (EPO); pattern recognition receptors (PRRs); cytokines; chemokines; red blood cells and haemoglobin
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Chin, V.-K.; Foong, K.-J.; Maha, A.; Rusliza, B.; Norhafizah, M.; Chong, P.P. Multi-Step Pathogenesis and Induction of Local Immune Response by Systemic Candida Albicans Infection in an Intravenous Challenge Mouse Model. Int. J. Mol. Sci. 2014, 15, 14848-14867.

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