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.
Pawlowski
S W
SW
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
Calabrese
G
G
Kolling
G L
GL
Platts-Mills
J
J
Freire
R
R
AlcantaraWarren
C
C
Liu
B
B
Sartor
R B
RB
Guerrant
R L
RL
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