Cardiac failure in C5-deficient A/J mice after Candida albicans infection.
The effect of a deficiency in the C5 component of complement on the pathophyisology of infection with the fungal pathogen Candida albicans was studied by using the A/J inbred mouse strain and the BcA17 congenic mouse strain. Acute infection caused by intravenous injection of C. albicans blastospores is associated with rapid fungal replication in the heart, brain, and, in particular, kidneys of C5-deficient mice. Histological studies and analysis of markers for tissue damage indicated that the heart is the organ that is most affected and that it ultimately fails in C5-deficient mice. In A/J and BcA17 mice, tissue damage is associated with (i) cellular infiltration in the heart, which is not seen in the kidney despite the higher fungal load in the latter organ, and (ii) a very strong inflammatory response, including elevated levels of many cytokines and chemokines. This results in cardiomyopathy, which is associated with elevated levels of creatine kinase and cardiac troponin I in the circulation. Damage to the cardiac muscle is associated with metabolic changes, including hypoglycemia, decreased lipid utilization resulting in elevated levels of cardiac triglycerides, and unproductive glucose utilization linked to a dramatic increase in the level of pyruvate dehydrogenase kinase 4 (Pdk4), a negative regulator of the pyruvate dehydrogenase complex.
Mullick
Alaka
A
Biotechnology Research Institute, National Research Council, 6100 Royalmount Avenue, Montréal, Québec, Canada H4P 2R2. alaka.mullick@cnrc-nrc.gc.ca
Leon
Zully
Z
Min-Oo
Gundula
G
Berghout
Joanne
J
Lo
Rita
R
Daniels
Eugene
E
Gros
Philippe
P
D000818:Animals; D002176:Candida albicans / Q000472:pathogenicity*; D002177:Candidiasis / Q000150:complications*; D003182:Complement C5 / Q000172:deficiency*; D003433:Crosses, Genetic; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D006321:Heart / Q000382:microbiology; D006331:Heart Diseases / Q000209:etiology*; D007249:Inflammation; D051379:Mice; D020297:Mice, Congenic; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism
D003182:Complement C5; D016207:Cytokines; D011506:Proteins