Murine model of Clostridium difficile infection with aged gnotobiotic C57BL/6 mice and a BI/NAP1 strain.
The increased incidence and severity of Clostridium difficile infection (CDI) in older adults (age, ≥65 years) corresponds with the emergence of the BI/NAP1 strain, making elucidation of the host immune response extremely important. We therefore infected germ-free C57BL/6 mice aged 7-14 months with a BI/NAP1 strain and monitored the mice for response. Infected mice were moribund 48-72 h after infection and developed gross and histological cecitis and colitis and elevated concentrations of keratinocyte chemoattractant, interleukin 1β, monocyte chemotactic protein 1, and granulocyte colony-stimulating factor and decreased levels of interferon γ, interleukin 12 p40, interleukin 12 p70, and interleukin 10 compared with controls. We conclude that aged, germ-free C57BL/6 mice are susceptible to fulminant CDI from a BI/NAP1 strain and represent a novel model to further elucidate the host immune response to acute CDI.
Center For Global Health, Division of Infectious Diseases and International Health, Department of Internal Medicine, University of Virginia, Charlottesville, VA 22908, USA. swpawlowski@hotmail.com
S W
SW
Pawlowski
G
G
Calabrese
G L
GL
Kolling
J
J
Platts-Mills
R
R
Freire
C
C
AlcantaraWarren
B
B
Liu
R B
RB
Sartor
R L
RL
Guerrant
D000818:Animals; D016360:Clostridioides difficile / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity*; D003106:Colon / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D005856:Germ-Free Life; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D053711:Interleukin-12 Receptor beta 1 Subunit / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL
D053711:Interleukin-12 Receptor beta 1 Subunit; D053583:Interleukin-1beta; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D007371:Interferon-gamma