A Staphylococcus aureus mouse keratitis topical infection model: cytokine balance in different strains of mice.
Staphylococcus is a leading cause of the potentially blinding disease microbial keratitis. Even with the use of antibiotic therapy, the host inflammatory response continues to damage the cornea, which may lead to blindness. Manipulation of the host response may help improve patient outcome from this devastating disease. We aim to understand the contribution of the host response to Staphylococcus aureus infection. A S. aureus keratitis mouse model was developed in both C57BL/6 and BALB/c mice using two different strains of S. aureus (8325-4 and Staph 38). Twenty-four hours postinfection, mice were killed and eyes were harvested for enumeration of bacteria, polymorphonuclear leucocytes, chemokines and cytokines. The laboratory strain 8325-4 was not as virulent as the clinical isolate Staph 38. In vitro data showed a 250-fold increase in invasion of human corneal epithelial cells by Staph 38 compared to 8325-4. BALB/c mice were susceptible to S. aureus infection whereas C57BL/6 mice were resistant. The resistant C57BL/6 mice were polarized towards a Th2 response, which may be protective for these mice. IL-4, IL-10 and IL-6 were elevated significantly in C57BL/6 mice infected with Staph 38 (P < 0.05). Macrophage inflammatory peptide (MIP)-2 was also significantly elevated in C57BL/6 mice (P < 0.001). The susceptible BALB/c mice had a muted cytokine response, which suggests that S. aureus might be 'walled off' during infection and might avoid host defences. IL-4, IL-10 and IL-6 cytokines may be protective during Gram-positive corneal infection and therefore may be useful for adjunct therapies in the treatment of this disease.
Hume
Emma B H
EB
The School of Optometry and Vision Science, The University of New South Wales, Australia.
Cole
Nerida
N
Khan
Shamila
S
Garthwaite
Linda L
LL
Aliwarga
Yulina
Y
Schubert
Tracey L
TL
Willcox
Mark D P
MD
D000818:Animals; D002452:Cell Count; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005123:Eye / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D007634:Keratitis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000473:pathology; D013203:Staphylococcal Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D013211:Staphylococcus aureus / Q000378:metabolism / Q000472:pathogenicity*; D010738:Type C Phospholipases / Q000378:metabolism; D014774:Virulence
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D016207:Cytokines; C074302:keratinocyte-derived chemokines; D010738:Type C Phospholipases