[Immunopathological mechanism of spleen damage in acute disseminated MCMV infection].
OBJECTIVE
To explore the immunopathological mechanism of spleen damage in acute disseminated infection of murine cytomegalovirus (MCMV) in vivo by observing the association of virus titers and the expressions of caspase-1 and pro-inflammatory factors (IL-1β and IL-18) with the degree of pathological damage of the spleen.


METHODS
BALB/c mice (n=24) were randomly divided into 2 groups (n=12 per group),  experimental group and control group. The control mice were sham-infected. The experimental mice were infected with  MCMV Smith for establishing the models of acute disseminated MCMV infection. Three mice of each group were randomly chosen to be killed on day 3,  7,  14 and 28 after infection,  respectively. Viral titers in the spleen tissues were determined using a standard plaque assay;   the expression of caspase-1 in the splenocytes was detected by Western blot;   the expressions of IL-1β and IL-18 in the spleen tissues were observed by immunohistochemical staining;   the degree of spleen histological damage was observed by HE staining and graded by a semiquantitative method.


RESULTS
Viral titers in the spleen peaked on day 3,  but quickly diminished on day 7 and virus was not detected in the spleen on day 14 after infection. Compared with the normal control group,  the protein levels of caspase-1 in MCMV-infected mice were markedly elevated on day 3 (P<0.01),  and then dropped slowly;   the expressions of IL-1β and IL-18 in the spleen tissues gradually increased to the climax on day 7,  then decreased on day 14 and turned to the normal on day 28. However,  the pathological condition of the spleen in infected mice deteriorated gradually until day 14,  and then showed obviously the signs of recovery on day 28. The spleen damage was aggravated following the elevation of IL-1β and IL-18 expressions and alleviated after they declined.


CONCLUSIONS
MCMV infection would stimulate the increase of caspase-1 expression and the production of pro-inflammatory factors (IL-1β and IL-18). IL-1β and IL-18 not only exert antiviral effect,  but also might be involved in the immunopathological injury of spleen tissue during the acute disseminated MCMV infection.
Department of Pediatrics, Huazhong University of Science and Technology, Wuhan, China. lingling2987@126.com
Ling-ling
LL
Liu
Xu-fang
XF
Li
Xing-lou
XL
Liu
Sai-nan
SN
Shu
Ge
G
Li
Feng
F
Fang
D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology*; D013154:Spleen / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D019562:Viral Load
D020382:Interleukin-18; D053583:Interleukin-1beta; D020170:Caspase 1