Dynamic expression of chemokines and the infiltration of inflammatory cells in the HSV-infected cornea and its associated tissues.
BACKGROUND
The chemotactic signals regulating cell trafficking in the herpes simplex virus type 1 (HSV-1) infected cornea are well documented, however, those in the cornea-associated tissues, such as the trigeminal ganglion (TG) and draining lymph nodes (LNs), are largely unknown.


OBJECTIVE
To examine chemokine expression and subsequent cell infiltration in the HSV-1 infected cornea and its associated tissues.


METHODS
Eight-week-old female BALB/c mice were infected with 10 mu l HSV-1 (CHR3 strain: 5 x 106 PFU/ml) by corneal scarification. Total RNAs were extracted from the corneas, TGs, and LNs at pre-inoculation, 3 days post-inoculation (P.I.) and 7 days P.I. The mRNA for 28 different chemokines in the extracts was amplified by RT-PCR. Infiltrating cells were identified by immunohistochemistry.


RESULTS
After the HSV-1 infection, the corneal stroma became edematous by infiltrated cells under the eroded epithelium. The TG and LNs were markedly swollen. The cornea was infiltrated with granulocytes and CD11b+ cells at 3 days P.I., followed by CD4+ and CD8+ T cells at 12 days P.I. In the TG, CD11b+ cells, but no granulocytes, infiltrated throughout the observation period. T cells migrated into the TG earlier than into the cornea. Gene expressions of neutrophil-attracting chemokines (CXCL1, 2, 3, and 5) increased in the cornea, but they did not enhance in the TG or LNs. On the other hand, gene expressions of chemokines which attract CD11b+ cells such as CCL2, 8, 7, 12, CCL3, 4, and CCL5, increased in the cornea and TG with its peak at 3 days P.I. Gene expressions of chemokines those work on T cells and B cells, such as CCL19, CCL21, CXCL9, CXCL13, CXCL10, XCL1, and CXCL16, were up-regulated and peaked at 3 days P.I. in the cornea and in the TG. Thus, pattern of chemokine gene expression was similar in the cornea and in the TG. On the contrary, gene expressions of chemokines in the draining LNs affecting CD11b+ cells and T cells were temporarily down-regulated.


CONCLUSIONS
Upon HSV-1 infection, dynamic gene expression of chemokines was observed not only in the inoculated cornea but also in its associated tissues.
Araki-Sasaki
Kaoru
K
Molecular and Cellular Recognition, Osaka University Graduate School of Medicine, Osaka, Japan. sasakis@sa2.so-net.ne.jp
Tanaka
Toshiyuki
T
Ebisuno
Yukihiko
Y
Kanda
Hidenobu
H
Umemoto
Eiji
E
Hayashi
Kozaburo
K
Miyasaka
Masayuki
M
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002465:Cell Movement; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006098:Granulocytes / Q000502:physiology; D018259:Herpesvirus 1, Human; D007124:Immunoenzyme Techniques; D016849:Keratitis, Herpetic / Q000235:genetics* / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology*; D008198:Lymph Nodes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012668:Trigeminal Ganglion / Q000378:metabolism*
D039481:CD11b Antigen; D018925:Chemokines; D012333:RNA, Messenger