A defective Th1 response of the spleen in the initial phase may explain why splenectomy helps prevent aListeriainfection

Abstract

SummaryListeria 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 ¥ ¥ ¥ ¥ 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-g g g g 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-g g g g while spleen MNC did not, whereas spleen leucocytes at 24 h after Listeria challenge did. Consistently, the IFN-g g g g 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.

Interleukin‐18 Protects Splenectomized Mice from LethalStreptococcus pneumoniaeSepsis Independent of Interferon‐γ by Inducing IgM Production

“…These finding indicate that S. pneumoniae escapes the hostdefense mechanism (both cellular immunity and humoral immunity) by inhibiting IFN-g production by NK cells and NKT cells as well as IL-18 production by Kupffer cells/macrophages via mutually independent mechanisms. We have recently reported that L. monocytogenes uses Th-1-defective spleen for its initial growth and, in contrast to encapsulated bacterial infection, splenectomy thereby inhibits Listeria infection [36]. Taken together with the results of the present study, it appears that each bacterium may have means to escape the host-defense mechanism.…”

“…Because we previously reported that IL-18 treatment increases serum or tissue IFN-g levels and improves the survival rate of mice infected with either Escherichia coli or Listeria monocytogenes by up-regulating IFNg [16,28,36], the splenectomized mice were thus ip injected with IL-18 at 10, 12, and 14 days after the splenectomy. At 2 h after the last IL-18 injection, the mice were challenged with S. pneumoniae ( cfu).…”

Which is the best? Palliative Radiation Therapy to Spleen or Splenectomy

“…In several studies of patients with lymphomas and hematologic malignancies, when spleen was irradiated at a dose of 12-40 Gy (2 Gy fractions/day), deterioration was shown in hematologic functions such as iltration and storage [16,18]. In several studies of patients with lymphomas and hematologic malignancies, when spleen was irradiated at a dose of 12-40 Gy (2 Gy fractions/day), deterioration was shown in hematologic functions such as iltration and storage [10,18,21]. During histopathological examination of the spleen after splenic RT to Hodgkin Lymphoma, changes in both white and red pulp and vascular structures were seen [32].…”

“…It is mostly seen in the irst two years after splenectomy and have high mortality rate of between 50-60% [4,5,13,[16][17][18]. Streptococcus pneumoniae, Haemophilus in luenzae and Neisseria meningitidis are the most common encapsulated microorganisms that have been found to be responsible for sepsis after splenectomy [19][20][21][22][23]. In blood culture of many patients with suspected sepsis, gram positive bacterium Streptococcus pneumoniae has been isolated in 50-90% of the time [23,25].…”

“…At this point, besides antibiotic effect, it may be necessary to strengthen the immune response. According to guidelines, in order to reduce morbidity and mortality, patient education, immunization and lifelong on-demand antimicrobial therapy are recommended [16,21,23,[26][27][28].…”