Impairment of T Cell‐Mediated Immunity to <i>Listeria monocytogenes</i> in Pregnant Mice

Sano, Mitsuru; Mitsuyama, Masao; Watanabe, Yoh-ichi; Nomoto, Kikuo

doi:10.1111/j.1348-0421.1986.tb00931.x

Cited by 19 publications

(10 citation statements)

References 38 publications

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“…This diminution in immunoreactivity helps protect the fetus from rejection (31, 33) but increases maternal susceptibility to infection by pathogens such as listeria (24,35). Previous studies established that CpG ODN stimulate the innate immune system of normal adult animals, thereby improving host resistance to infection by a variety of bacterial, viral, and parasitic pathogens (6,7,15,19,23,27,29,30,32,42).…”

Section: Discussionmentioning

confidence: 99%

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CpG Oligodeoxynucleotides Improve the Survival of Pregnant and Fetal Mice followingListeria monocytogenesInfection

et al. 2004

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Listeria infection during pregnancy can cause the death of both mother and fetus. Previous studies established that immunostimulatory CpG oligodeoxynucleotides (ODN) increase the resistance of healthy adult mice to many infectious pathogens, including Listeria monocytogenes. This study examines whether the innate immune response elicited by CpG ODN can reduce the susceptibility of pregnant mice to lethal listeria challenge. The results indicate that CpG ODN treatment significantly improves maternal survival and reduces pathogen transmission to offspring. CpG ODN administered during pregnancy did not induce abortion, birth defects, or reduce the size or health of litters. These findings suggest that CpG ODN may provide a safe and effective means of improving the health of mothers and fetuses during pregnancy.Pregnancy leads to a generalized suppression of the adaptive immune system, typified by significantly decreased cell-mediated immunity and reduced Th1 responsiveness (25,31,33,38,39). This immunosuppressed state prevents maternal rejection of the fetus (31, 33) but has the unfortunate consequence of increasing maternal susceptibility to certain infectious agents (24,35).Listeria monocytogenes is a gram-positive intracellular bacterium that is a common cause of maternal infection (37,40). This pathogen can be transmitted from mother to fetus, substantially increasing the risk of abortion, stillbirth, congenital malformations, and neonatal mortality and morbidity (2,26,40). In the absence of preexisting maternal vaccination, there is no widely accepted strategy for preventing infection, since immunomodulatory therapy runs the risk of adversely affecting the neonate.Rapid activation of the innate immune system can limit the early spread of listeriae, allowing the host to develop sterilizing adaptive immunity (17, 21). The innate immune system is activated when Toll-like receptors (TLR) expressed by immune cells recognize pathogen-associated molecular patterns (PAMPs) expressed by infectious microorganisms (1,28). CpG motifs present in bacterial DNA act as PAMPs (11,18,22,41), interacting with TLR-9 to trigger an innate immune response in which lymphocytes, dendritic cells, and macrophages are stimulated to produce immunoprotective cytokines and chemokines (3,9,11,14,18,22,34,36). Treatment with CpG oligodeoxynucleotides (ODN) can improve the resistance of normal adult mice to a variety of bacterial, viral and parasitic pathogens (6,7,15,23,30,32,42). This immunoprotective effect peaks several days after CpG ODN administration and persists for several weeks (6,19,23).The current study was undertaken to determine whether CpG ODN can be of benefit during pregnancy, improving survival after listeria infection. The results indicate that CpG ODN treatment effectively stimulates the innate immune system of pregnant mice, improves maternal survival, and prevents pathogen transmission to offspring. MATERIALS AND METHODSReagents. CpG (GCTAGACGTTAGCGT) and control (GCTAGAGCTTA GGCT) phosphorothioate ODN were synthesized at...

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Section: Discussionmentioning

confidence: 99%

“…This immunosuppressed state prevents maternal rejection of the fetus (31,33) but has the unfortunate consequence of increasing maternal susceptibility to certain infectious agents (24,35).…”

mentioning

confidence: 99%

CpG Oligodeoxynucleotides Improve the Survival of Pregnant and Fetal Mice followingListeria monocytogenesInfection

et al. 2004

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“…Although granulocytes, macrophages as well as CD4+ and CD8+ T cells were recruited to the liver, these cell populations were unable to restrict growth of L. monocytogenes. In vitro studies have revealed that supernatant from spleen cells of pregnant mice stimulated with L. monocytogenes antigen failed to stimulate macrophages for an appropriate killing of tumor cells [44]. In addition, Sano et al [44] noticed reduced T-cell responses in Listeria-infected pregnant mice as evidenced by a lower delayed-type hypersensitivity (DTH) reaction than in virgin animals.…”

Section: Discussionmentioning

confidence: 98%

“…In vitro studies have revealed that supernatant from spleen cells of pregnant mice stimulated with L. monocytogenes antigen failed to stimulate macrophages for an appropriate killing of tumor cells [44]. In addition, Sano et al [44] noticed reduced T-cell responses in Listeria-infected pregnant mice as evidenced by a lower delayed-type hypersensitivity (DTH) reaction than in virgin animals. These impaired cellular immune responses in pregnant mice may be explained by our observation of a reduced expression of TNF, IFN-γ, IL12p40, and iNOS in liver and of IFN-γ in serum, which are all of key importance for an effective control and elimination of L. monocytogenes [3,5,13,18,19,20,25,43].…”

Section: Discussionmentioning

confidence: 98%

Effects of pregnancy-associated Listeria monocytogenes infection: necrotizing hepatitis due to impaired maternal immune response and significantly increased abortion rate

et al. 2002

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The impact of L. monocytogenes infection on maternal immune responses as well as on the outcome of pregnancy was studied in a murine model of pregnancy-associated listeriosis. Mice infected i.v. with L. monocytogenes at day 15 of pregnancy showed a significantly impaired bacterial elimination, which resulted in a severe necrotizing hemorrhagic hepatitis. The aggravated course of the infection could be attributed to a suppressed transcription and production of anti-listerial, pro-inflammatory cytokines and chemokines, namely interferon-gamma, tumor necrosis factor, interleukin-12p40, inducible nitric oxide synthase, murine monokine induced by interferon-gamma, and interferon-gamma-inducible protein-10. In addition, listeriosis significantly increased the abortion rate. Infection of the placenta and fetuses was characterized by placental and fetal necrosis with unrestricted bacterial multiplication. A weak transcription of anti-listerial cytokines in the placenta in the absence of a cellular immune response could not prevent the fatal outcome of pregnancy-associated listeriosis.

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“…Pregnancy leads to a generalized suppression of the adaptive immune system, typified by significantly decreased cell-mediated immunity and reduced Th1 responsiveness [21,33,34], and this immunosuppressed state prevents maternal rejection of the fetus but has the unfortunate consequence of increasing maternal susceptibility to certain infectious agents [16,23]. This is considered to be the reason that pregnant IFN-γ knockout mice died more rapidly due to B. abortus infection than non-pregnant IFN-γ knockout mice.…”

Section: Discussionmentioning

confidence: 99%

Regulated upon Activation Normal T-Cell Expressed and Secreted (RANTES) Contributes to Abortion Caused by Brucella abortus Infection in Pregnant Mice

et al. 2008

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ABSTRACT. Brucella abortus (B. abortus) is a facultative intracellular pathogen that can survive inside macrophages and trophoblast giant cells, and the causative agent of brucellosis. In the present study, we found that production of regulated upon activation normal T-cell expressed and secreted (RANTES) due to B. abortus infection contributes to abortion in pregnant mice. B. abortus infected pregnant interferon-γ (IFN-γ) knockout mice died within 15 days of infection, but non-pregnant IFN-γ knockout mice were still alive. With infection by wild type B. abortus, a large amount of RANTES production was observed in pregnant IFN-γ knockout mice, and induction of RANTES was also observed in normal pregnant mice infected with the wild type, but not in those infected with the intracellular replication-defective mutant. Production of RANTES and IFN-γ were inhibited in mice inoculated with the respective RANTES or IFN-γ antibody. Neutralization of RANTES, induced by B. abortus infection, served to prevent abortion. These results indicate that the production and function of RANTES are correlated with IFN-γ in pregnant mice infected with B. abortus.

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Impairment of T Cell‐Mediated Immunity to Listeria monocytogenes in Pregnant Mice

Abstract: In order to study pregnancy-induced changes in cell-mediated immunity to Listeria monocytogenes, acquired resistance and T cell functions in pregnant mice were compared with those in nonpregnant mice after immunization with viable listerial cells.

Cited by 19 publications

References 38 publications

CpG Oligodeoxynucleotides Improve the Survival of Pregnant and Fetal Mice followingListeria monocytogenesInfection

CpG Oligodeoxynucleotides Improve the Survival of Pregnant and Fetal Mice followingListeria monocytogenesInfection

Effects of pregnancy-associated Listeria monocytogenes infection: necrotizing hepatitis due to impaired maternal immune response and significantly increased abortion rate

Regulated upon Activation Normal T-Cell Expressed and Secreted (RANTES) Contributes to Abortion Caused by Brucella abortus Infection in Pregnant Mice

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