Purchase this article with an account.
Katie M. Hudson, Dan J. Carr; Cxcl1 Contributes To Host Resistance Following Pseudomonas Aeruginosa Corneal Infection But Not To Herpes Simplex Virus Type 1. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6129.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To determine the role of CXCL1 in the recruitment of leukocytes and resistance comparing acute herpes simplex virus type 1 (HSV-1) and Pseudomonas aeruginosa corneal infections.
Viral titer of HSV-1 infected wild-type (WT) and CXCL1-deficient (CXCL1-/-) mice was assessed on days 3 and 7 post-infection (PI). Bacterial load was determined 24 hours following P. aeruginosa infection. Recruitment of neutrophils (F4/80- Gr1+), macrophages (F4/80+ Gr1-), inflammatory monocytes (F4/80+ Gr1+) and NK cells (NK1.1+ CD3-) to the cornea following either HSV-1 or P. aeruginosa infection was determined using flow cytometry. Interferon-gamma (IFN-γ), CXCL1, CXCL2, CCL2, and CCL5 protein levels in infected corneas were assessed by luminex-based suspension arrays. Histological analysis using hematoxylin and eosin (H&E) staining was performed on infected eyes. Confocal microscopy was utilized to assess recruitment of neutrophils to HSV-1 lesions. Optical coherence tomography (OCT) was used to visualize cornea thickening during acute P. aeruginosa infection.
HSV-1 infected WT and CXCL1-/- mice exhibited similar viral loads in the cornea. Flow cytometry, H&E staining, and confocal analysis revealed similar leukocyte recruitment to the cornea and neutrophil recruitment to HSV-1 lesions. However, there was a significant increase in P. aeruginosa recovered from CXCL1-/- corneas as compared to WT. H&E staining and OCT analysis revealed impaired leukocyte recruitment to the central cornea and earlier corneal thickening in CXCL1-/- mice, respectively. IFN-γ, CXCL1, CCL2, and CCL5 protein levels were similar between WT and CXCL1-/- corneas following HSV-1 or P. aeruginosa infection. However, CXCL2 levels were significantly reduced in the CXCL1-/- corneas following either infection.
These findings demonstrate that CXCL1 expression is not required for neutrophil recruitment to HSV-1 lesions or viral clearance during acute ocular infection. However, the loss of CXCL1 significantly impaired the host’s ability to clear P. aeruginosa from the cornea associated with a skewed recruitment pattern of neutrophils. Furthermore, loss of CXCL1 significantly reduced CXCL2 expression following either infection, suggesting neither chemokine is required for viral clearance, but either may be important for anti-bacterial defense.
This PDF is available to Subscribers Only