A defective Th1 response of the spleen in the initial phase may explain why splenectomy helps prevent a Listeria infection.
Listeria monocytogenes (Listeria) are known to grow and proliferate in the liver while a splenectomy induces host resistance against a Listeria infection despite the fact that a splenectomy inhibits the Th1 response. Therefore, the mechanism by which a splenectomy helps to prevent the growth of Listeria still remains to be elucidated. After an i.v. challenge of Listeria (1 x 10(6) CFU) in C57BL/6 mice, Listeria rapidly increased in the spleen but not in the liver until 48 h. However, after this initial phase, Listeria remarkably grew in the liver. In contrast, when the mice received a splenectomy beforehand, no remarkable growth of Listeria in the liver was observed after Listeria challenge despite the fact that serum IFN-gamma and IL-12 levels at 24 h after Listeria challenge were significantly lower than those in the sham mice. However, the liver leucocytes from mice by 6 h after infection produced a substantial amount of IFN-gamma while spleen MNC did not, whereas spleen leucocytes at 24 h after Listeria challenge did. Consistently, the IFN-gamma and IL-12 levels in the tissue homogenates of the spleen were significantly lower than in those of the liver until 6 h after infection. This defective spleen Th1 response in the early phase of Listeria infection was corrected by an IL-18 i.p. injection just after the Listeria challenge. Our findings suggest that Listeria exploit the defective Th1 environment of the spleen in the initial phase and afterwards overcome the host defense mechanism of the liver.
Kuranaga
N
N
Department of Microbiology, National Defense Medical College, Tokorozawa, Japan.
Kinoshita
M
M
Kawabata
T
T
Shinomiya
N
N
Seki
S
S
D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis / Q000097:blood; D018664:Interleukin-12 / Q000032:analysis / Q000097:blood; D020382:Interleukin-18 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000517:prevention & control*; D008099:Liver / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology* / Q000382:microbiology; D013156:Splenectomy / Q000379:methods*; D018417:Th1 Cells / Q000276:immunology*
D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma