A role for tumor necrosis factor-alpha in experimental Bacillus cereus endophthalmitis pathogenesis.
OBJECTIVE
To determine the contribution of tumor necrosis factor-alpha (TNFalpha) in the pathogenesis of experimental Bacillus cereus endophthalmitis.


METHODS
Experimental B. cereus endophthalmitis was induced in wild-type control (B6.129F1) and age-matched homozygous TNFalpha knockout mice (TNFalpha(-/-), B6.129S6-Tnf(tm1Gk1)/J). At various times after infection, eyes were analyzed by electroretinography and were harvested for quantitation of bacteria, myeloperoxidase, proinflammatory cytokines and chemokines, and histologic analysis.


RESULTS
B. cereus replicated more rapidly in the eyes of TNFalpha(-/-) mice than in the eyes of B6.129F1 mice. Retinal function decreased more rapidly in TNFalpha(-/-) mice than in B6.129F1 mice. Retinal layers were not as structurally intact at 6 and 12 hours after infection in TNFalpha(-/-) eyes as in B6.129F1 eyes. Histologic analysis suggested less polymorphonuclear leukocyte (PMN) infiltration into the vitreous of TNFalpha(-/-) mice than of B6.129F1 mice. B6.129F1 eyes also had greater myeloperoxidase concentrations than did eyes of TNFalpha(-/-) mice. In general, concentrations of proinflammatory cytokines and chemokines (IL-1beta, KC, IL-6, and MIP-1alpha) were greater in eyes of TNFalpha(-/-) mice than of B6.129F1 mice.


CONCLUSIONS
TNFalpha is important to intraocular pathogen containment by PMNs during experimental B. cereus endophthalmitis. In the absence of TNFalpha, fewer PMNs migrated into the eye, facilitating faster bacterial replication and retinal function loss. Although greater concentrations of proinflammatory cytokines were synthesized in the absence of TNFalpha, the resultant inflammation was diminished, and an equally devastating course of infection occurred.
Ramadan
Raniyah T
RT
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Moyer
Andrea L
AL
Callegan
Michelle C
MC
D000818:Animals; D001409:Bacillus cereus / Q000502:physiology*; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D004596:Electroretinography; D009877:Endophthalmitis / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D015818:Eye Infections, Bacterial / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012160:Retina / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014822:Vitreous Body / Q000276:immunology / Q000382:microbiology
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase