IFN-α-driven CCL2 production recruits inflammatory monocytes to infection site in mice.
Herpes simplex virus type 1 (HSV-1) is the leading cause of corneal blindness in the developed world due to reactivation of infectious virus and the subsequent immune response. The innate response that facilitates viral control in the cornea is currently unknown. In the present study using a mouse chimera model, we found that a bone marrow component is crucial in inhibiting viral replication and identified inflammatory monocytes (F4/80(+) Gr1(+)) as the responsible cell. CCL2 was critical for recruiting inflammatory monocytes, and a loss of this chemokine in CCL2(-/-) mice resulted in a loss of viral containment and inflammatory monocyte recruitment. To confirm these results, clodronate depletion of inflammatory monocytes resulted in elevated viral titers. Furthermore, siRNA targeting the innate sensor p204/IFI-16 resulted in a loss of CCL2 production. In conclusion, CCL2 expression driven by IFI-16 recognition of HSV-1 facilitates the recruitment of inflammatory monocytes into the cornea proper to control viral replication.
Department of Microbiology, Immunology University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
C D
CD
Conrady
M
M
Zheng
N A
NA
Mandal
N
N
van Rooijen
D J J
DJ
Carr
D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D003315:Cornea / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016898:Interferon-alpha / Q000378:metabolism*; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D014779:Virus Replication
D018932:Chemokine CCL2; D016898:Interferon-alpha; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D009569:Nitric Oxide