The role of eosinophils and neutrophils in helminth-induced keratitis.
OBJECTIVE
Intrastromal injection of mice with antigens from the parasitic helminth that causes river blindness (Onchocerca volvulus) induces eosinophil recruitment to the corneal stroma at the time of maximum corneal opacification and neovascularization. The present study was conducted to examine the role of eosinophils and neutrophils in onchocercal keratitis in control C57Bl/6 mice and in interleukin-5 gene knockout (IL-5(-/-)) mice.


METHODS
C57Bl/6 and IL-5(-/-) mice were immunized subcutaneously and injected intrastromally with soluble O. volvulus antigens. Mice were killed at various times thereafter. Development of keratitis was assessed by slit lamp examination, and inflammatory cells in the cornea were identified by immunohistochemistry.


RESULTS
A biphasic recruitment of inflammatory cells was observed in C57Bl/6 mice; neutrophils predominated during the first 72 hours after intrastromal injection and subsequently declined, whereas eosinophil recruitment increased as time elapsed and comprised the majority (90%) of cells in the cornea by day 7. In contrast, neutrophils were the predominant inflammatory cells in IL-5(-/-) mice at early and late time points and were associated with extensive stromal damage and corneal opacification and neovascularization. Eosinophils were not detected in these mice at any time.


CONCLUSIONS
In the absence of eosinophils, neutrophils can mediate keratitis induced by helminth antigens. Together with the early neutrophilic infiltrate in control animals, these observations indicate that neutrophils have an important role in onchocercal keratitis.
Pearlman
E
E
Department of Medicine, Case Western Reserve University, and University Hospitals of Cleveland, Ohio 44106-4983, USA.
Hall
L R
LR
Higgins
A W
AW
Bardenstein
D S
DS
Diaconu
E
E
Hazlett
F E
FE
Albright
J
J
Kazura
J W
JW
Lass
J H
JH
D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage; D003315:Cornea / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D016510:Corneal Neovascularization / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D003318:Corneal Opacity / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004804:Eosinophils / Q000502:physiology*; D005260:Female; D007124:Immunoenzyme Techniques; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D007634:Keratitis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D017181:Onchocerca volvulus / Q000276:immunology*; D015827:Onchocerciasis, Ocular / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000378:metabolism
D000947:Antigens, Helminth; D016207:Cytokines; D017931:DNA Primers; D015848:Interleukin-5