Respiratory infection with Francisella novicida induces rapid dystrophic cardiac calcinosis (DCC).
Francisella tularensis causes pulmonary tularemia and death in humans when left untreated. Here, using a novel aerosol infection model, we show that acute pulmonary Francisella novicida infection not only causes pneumonia and liver damage, but also induces dystrophic cardiac calcinosis (DCC) in BALB/c mice. C57BL/6 mice also develop pneumonia and hepatic damage, but fail to develop DCC. Development of DCC in BALB/c mice is associated with significant induction of RANKL but not osteopontin in their organs. Depletion of lung macrophages prior to infection markedly reduces pericarditis and calcification in BALB/c mice but does not increase their susceptibility to infection.
Roth
Kimberly M
KM
Department of Microbiology, The Ohio State University, Columbus, OH 43210, USA.
Oghumu
Steve
S
Satoskar
Anjali A
AA
Gunn
John S
JS
van Rooijen
Nico
N
Satoskar
Abhay R
AR
D000818:Animals; D002114:Calcinosis / Q000378:metabolism / Q000382:microbiology*; D009202:Cardiomyopathies / Q000378:metabolism / Q000382:microbiology*; D005260:Female; D005603:Francisella / Q000254:growth & development*; D016905:Gram-Negative Bacterial Infections / Q000378:metabolism* / Q000382:microbiology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000382:microbiology; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053495:Osteopontin / Q000096:biosynthesis / Q000235:genetics; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012141:Respiratory Tract Infections / Q000378:metabolism* / Q000382:microbiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D007375:Interleukin-1; D015850:Interleukin-6; D053245:RANK Ligand; D012333:RNA, Messenger; C506896:Spp1 protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin