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.
Highlights
Candida albicans is a major fungal pathogen that causes both mucocutaneous and disseminated infections, in debilitated or immunocompromised patients [1]
We studied the effect on the red blood cells and erythropoiesis as the fungus invades the bloodstream and elucidated the gene expression changes of the whole kidney, brain and spleen in response to C. albicans infection using a quantitative reverse transcriptase polymerase chain reaction array platform
The tissue distribution of C. albicans in systemically infected BALB/c female mice was determined by culturing the kidneys, lungs, livers, spleens and brains homogenates at 24, 72, and 128 h (1, 3, and 7 days respectively) post infection
Summary
Candida albicans is a major fungal pathogen that causes both mucocutaneous and disseminated infections, in debilitated or immunocompromised patients [1]. C. albicans exhibits immense plasticity in its ability to colonize various microniches within the human host, causing a wide range of infections. Systemic infection with Candida species, C. albicans often involves dissemination to multiple internal organs via hematogenous spread and is often life threatening, with the overall prognosis comparable to a septic shock and multiple organ failure [2]. Invasive Candida infections are increasing in incidence in intensive care units of hospitals, they present problems in terms of treatment and management [3]. The epidemiology of the infections could be attributed to contaminated vascular catheters or parenteral nutrition tubings and other biomedical devices which have Candida biofilm growth
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