Natural Killer Cell Responses to Infections in Early Life

Guilmot, Aline; Hermann, Emmanuel; Braud, Véronique M.; Carlier, Yves; Truyens, Carine

doi:10.1159/000323934

Cited by 72 publications

(61 citation statements)

References 128 publications

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“…T cells from neonates congenitally infected with T. cruzi [4]. A concomitant production of IFN-c by NK cells, besides T cells, cannot be excluded since such cells are also present in eDCs preparations [58,59].…”

Section: Discussionmentioning

confidence: 99%

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Activation of cord blood myeloid dendritic cells by Trypanosoma cruzi and parasite-specific antibodies, proliferation of CD8+ T cells, and production of IFN-γ

Rodríguez

Carlier

Truyens

2011

Med Microbiol Immunol

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We previously reported that Trypanosoma cruzi, the agent of Chagas disease, induces in congenitally infected fetuses a strong, adult-like parasite-specific CD8(+) T cell response producing IFN-γ (Hermann et al. in Blood 100:2153-2158, 2002). This suggests that the parasite is able to overcome the immaturity of neonatal antigen presenting cells, an issue which has not been previously addressed. We therefore investigated in vitro the ability of T. cruzi to activate cord blood DCs and compared its effect to that on adult cells. We show that T. cruzi induces phenotypic maturation of cord blood CD11c(+) myeloid DCs (mDCs), by enhancing surface expression of CD40, CD80, and CD83, and that parasite-specific IgG purified from cord blood of neonates born to T. cruzi-infected mothers amplify such expression. CD83, considered as the best marker of mature DCs, reaches higher level on cord blood than on adult mDCs. Allo-stimulation experiments showed that T. cruzi-activated cord blood mononuclear cells enriched in DCs (eDCs) stimulate proliferation of cord blood and adult CD3(+) T cells to a similar extent. Of note, T. cruzi-activated eDCs from cord blood trigger more potent proliferation of CD8(+) than CD8(-) (mainly CD4(+)) adult T cells, a feature not observed with adult eDCs. T cell proliferation is associated with IFN-γ release and down-regulation of IL-13 production. These data show that T. cruzi potently activates human cord blood mDCs and endows eDCs to trigger CD8(+) T cell proliferation and favor type 1 immune response. Interestingly, maternal antibodies can strengthen the development of mature DCs that might contribute to overcome the immunological immaturity associated with early life.

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Section: Discussionmentioning

confidence: 99%

“…Cross-talk with other cells present in our assays, like NK cells, might also indirectly contribute to improve DC activation [76][77][78]. Arguing for this, T. cruzi is able to rapidly activate NK cells [59].…”

Section: Discussionmentioning

confidence: 99%

Activation of cord blood myeloid dendritic cells by Trypanosoma cruzi and parasite-specific antibodies, proliferation of CD8+ T cells, and production of IFN-γ

Rodríguez

Carlier

Truyens

2011

Med Microbiol Immunol

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“…Notably, other than activated T cells, NK cells are the only known source of IFN-␥ which shapes the pattern of innate and adaptive immune responses [26][27][28] . The innate immune response of NK cells against HIV is crucial both for the subsequent course of the infection and for the induction of an efficient adaptive response.…”

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confidence: 99%

HIV-1 Gag-Virus-Like Particles Induce Natural Killer Cell Immune Responses via Activation and Maturation of Dendritic Cells

Chang

Suzuki²,

Suzuki³

et al. 2011

J Innate Immun

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Despite the extensive efforts that have been made to combat acquired immune deficiency syndrome (AIDS), the number of people infected each year with human immunodeficiency virus type 1 (HIV-1) is still increasing worldwide, and a safe and effective vaccine to control HIV infection is urgently needed. Recently, the natural killer (NK) cell-mediated innate immune response, which represents the first line of defense against infections, has attracted attention for its role in combating HIV infection and disease progression. In the present study, we investigated the immunogenic ability of HIV-1 Gag-virus-like particles (Gag-VLPs) to induce NK cell immune responses in vitro and in vivo. Gag-VLPs efficiently activated human monocyte-derived dendritic cells (MDDCs), eliciting MDDC maturation with an associated increase in the surface expression of CD80, CD86 and MHC classes I and II, MDDC proliferation and proinflammatory cytokine production. Gag-VLP-treated MDDCs subsequently activated autologous NK cells, leading to their proliferation and production of interferon-γ and to the upregulation of NK cell cytotoxicity against YAC-1 cells and HIV-1-infected CD4⁺ T cells. In addition, we introduced a 2-phase immunization strategy in BALB/c mice to assess the role of DCs in the induction of NK cell immune responses by Gag-VLPs in vivo. Our findings reveal that Gag-VLPs efficiently activate DCs, which in turn induce innate and Gag-specific immune responses in NK cells.

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“…Brandstadter and Yang [18] provide an overview of how NK cells are activated in response to viral infections and continue to discuss the recruitment of activated NK cells to the site of infection, and then discuss NK cell effector mechanisms against virally infected cells. Covering an area that has not so often been reviewed in the past, Guilmot et al [19] discuss NK cell responses to infections in early life. They summarize the phenotype and functional abilities of NK cells from healthy infants, and NK cell responses against viral, bacterial and protozoan infections early in life.…”

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confidence: 99%