The corneal response to infection with Staphylococcus aureus in the absence of interleukin-4.
Interleukin-4 (IL-4) has previously been implicated in a protective response to Staphylococcus aureus corneal infection. Consequently, the specific role of IL-4 during S. aureus corneal infection was investigated using IL-4 gene knockout mice. The eyes of IL-4-/- mice and wild-type mice were challenged topically with S. aureus and examined at 24 h post-infection. Keratitis was examined clinically and histologically. Bacterial and polymorphonuclear leucocytes (PMN) numbers were enumerated and cytokine and chemokine levels determined by enzyme-linked immunosorbent assay. Exogenous IL-4 was administered to both IL-4-/- and wild-type mice and clinical parameters were determined. A lack of IL-4 resulted in a significant increase in clinical scores, pathology, bacterial load and neutrophil numbers. The absence of IL-4 also resulted in an upregulation of interferon (IFN)-gamma and a downregulation of IL-6, IL-10 and the chemokines KC and macrophage inflammatory protein-2. Administration of exogenous IL-4 to IL-4-/- mice was protective but time-dependent. This study highlights the protective role of IL-4 during S. aureus infection and emphasizes the balance between IL-4 and IFN-gamma in achieving bacterial control and maintaining the integrity of the cornea. This information may lead to the development of novel therapeutic strategies potentially improving the prognosis for infection of this unique avascular site.
Cole
Nerida
N
Institute for Eye Research, University of New South Wales, Sydney, NSW 2052, Australia.
Hume
Emma B
EB
Khan
Shamila
S
Garthwaite
Linda
L
Schubert
Tracey
T
Reeve
Vivienne
V
Willcox
Mark D P
MD
D000818:Animals; D018925:Chemokines / Q000032:analysis; D015169:Colony Count, Microbial; D003315:Cornea / Q000276:immunology* / Q000382:microbiology; D016207:Cytokines / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D007634:Keratitis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000502:physiology*
D018925:Chemokines; D016207:Cytokines; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma