Mousepox conjunctivitis: the role of Fas/FasL-mediated apoptosis of epithelial cells in virus dissemination.
BALB/c mice infected with the Moscow strain of Ectromelia virus (ECTV-MOS) show a large number of apoptotic cells, and an influx of lymphoid cells in the epithelium and substantia propria of conjunctivae, respectively. The presence of ECTV-MOS antigens in the epithelium of conjunctivae significantly upregulates Fas in the epithelial layer and FasL in the suprabasal layer of conjunctiva. Inhibition of FasL with blocking antibodies in cultures of conjunctival cells isolated from ECTV-MOS-infected BALB/c mice showed that the Fas/FasL pathway is important in apoptosis of ECTV-MOS-infected cells. The results also showed that the presence of cytokines, in particular interferon (IFN)-gamma, upregulated expression of Fas. Interleukin (IL) 2, 4, 10 and IFN-gamma were produced at the peak of conjunctivitis (at day 15 of infection) with a predominance of IFN-gamma and a small, but significant, production of IL4 and IL10 compared with non-infected animals. These results suggest that not only is Fas/FasL expression in conjunctiva involved in elimination of migrating Fas+ cells but also plays an important role in the turnover of conjunctival epithelium and thus may be crucial for ECTV spreading to the surrounding environment.
Krzyzowska
Malgorzata
M
Immunology Laboratory, Division of Virology, Mycology and Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Ciszewskiego 8, 02-786 Warsaw, Poland.
Polanczyk
Magdalena
M
Department of Neuroimmunology, School of Medicine, Oregon Health Sciences University, Portland, OR 97201, USA.|Immunology Laboratory, Division of Virology, Mycology and Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Ciszewskiego 8, 02-786 Warsaw, Poland.
Bas
Monika
M
Immunology Laboratory, Division of Virology, Mycology and Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Ciszewskiego 8, 02-786 Warsaw, Poland.
Cymerys
Joanna
J
Immunology Laboratory, Division of Virology, Mycology and Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Ciszewskiego 8, 02-786 Warsaw, Poland.
Schollenberger
Ada
A
Immunology Laboratory, Division of Virology, Mycology and Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Ciszewskiego 8, 02-786 Warsaw, Poland.
Chiodi
Francesca
F
Microbiology and Tumor Biology Center, Karolinska Institute, Nobels väg 16, S-17177 Stockholm, Sweden.
Niemialtowski
Marek
M
Immunology Laboratory, Division of Virology, Mycology and Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Ciszewskiego 8, 02-786 Warsaw, Poland.
D000818:Animals; D017209:Apoptosis; D003228:Conjunctiva / Q000166:cytology / Q000473:pathology / Q000821:virology; D003236:Conjunctivitis, Viral / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D004481:Ectromelia virus / Q000472:pathogenicity* / Q000502:physiology; D004482:Ectromelia, Infectious / Q000503:physiopathology / Q000821:virology; D004847:Epithelial Cells / Q000502:physiology* / Q000821:virology; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism*
D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor