Abstract
Experimental models have established Panton–Valentine leukocidin (PVL) as a potential critical virulence factor during Staphylococcus aureus endophthalmitis. In the present study, we aimed to identify retinal cell targets for PVL and to analyze early retinal changes during infection. After the intravitreous injection of PVL, adult rabbits were euthanized at different time points (30 min, 1, 2, 4 and 8 h). PVL location in the retina, expression of its binding receptor C5a receptor (C5aR), and changes in Müller and microglial cells were analyzed using immunohistochemistry, Western blotting and RT-qPCR. In this model of PVL eye intoxication, only retinal ganglion cells (RGCs) expressed C5aR, and PVL was identified on the surface of two kinds of retinal neural cells. PVL-linked fluorescence increased in RGCs over time, reaching 98% of all RGCs 2 h after PVL injection. However, displaced amacrine cells (DACs) transiently colocalized with PVL. Müller and microglial cells were increasingly activated after injection over time. IL-6 expression in retina increased and some microglial cells underwent apoptosis 4 h and 8 h after PVL infection, probably because of abnormal nitrotyrosine production in the retina.
Highlights
Methicillin-resistant S. aureus (MRSA) places a significant burden on healthcare resources due to its resistance to antimicrobial treatment
Since this cell layer is composed of retinal ganglion cells (RGCs) and displaced amacrine cells (DACs), we investigated the exact target of Panton–Valentine leukocidin (PVL) using specific labeling for RGCs and DACs (Table 1)
C5a receptors are abundantly expressed in myeloid cells, but they are less expressed in non-myeloid cells
Summary
Methicillin-resistant S. aureus (MRSA) places a significant burden on healthcare resources due to its resistance to antimicrobial treatment. Recent studies have reported that PVL binds to human complement C5a receptor. Recent studies on humanized mice with C5aR showed the critical role played by PVL in the determination of necrotizing pneumonia and its severity[10,11]. There has been evidence of PVL targeting myeloid cells such as monocytes (M), macrophages (Mφ), and polymorphonuclear cells (PMNs), but not lymphocytes[12]. Another recent study showed that in vitro, PVL could target dorsal root neurons and cerebellum granular neurons[13]. Our purpose was to identify retinal cell targets for PVL and to analyze initial mechanisms that might support or indicate inflammation and inter-cellular communication. The results reported strongly suggest that PVL colocalized with two types of retinal neurons: displaced amacrine cells (DACs) very early in the translocation process, and retinal ganglion cells (RGCs), which triggered a glial reaction and an increase of IL-6 expression in the retina
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