CD4+ Valpha14 NKT cells play a crucial role in an early stage of protective immunity against infection with Leishmania major

Ishikawa, Hiroyuki; Hisaeda, Hajime; Taniguchi, Masaru; Nakayama, Toshinori; Sakai, Tohru; Maekawa, Yoichi; Nakano, Yoko; Zhang, Manxin; Zhang, Tianqian; Nishitani, Masaaki; Takashima, Mika; Himeno, Kunisuke

doi:10.1093/intimm/12.9.1267

Cited by 103 publications

(73 citation statements)

References 27 publications

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“…It has been shown that NKT cells play a crucial role in an early stages of protective immunity against infection with Leishmania major in mice (19). It has also been recently described that a subset of murine NKT cells is activated during L. donovani infection (20).…”

Section: Endritic Cells (Dcs)mentioning

confidence: 99%

Immature Human Dendritic Cells Infected with Leishmania infantum Are Resistant to NK-Mediated Cytolysis but Are Efficiently Recognized by NKT Cells

Campos-Martín

Colmenares

Gozalbo-López

et al. 2006

The Journal of Immunology

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Dendritic cells (DC) play an important role in innate and adaptive immunity, interacting with T cells, NK, and NKT cells. A critical step in the interaction of the parasitic protozoa Leishmania with their host is the evasion of both innate and adaptive immunity, producing a long-lasting chronic infection. There is growing evidence that these parasites can modify the Ag-presenting and immunoregulatory functions of DCs. The cells and mechanisms involved in innate immune response against Leishmania are still poorly understood. In this study, we investigated how Leishmania infantum infection affects DC interactions with NK and invariant NKT (iNKTs) cells in humans. We found that infected immature DCs (iDCs) do not up-regulate HLA class I molecules. Despite this, iDCs become resistant to killing mediated by autologous NK cells due to the up-regulation of HLA-E expression, which protects target cells from NK-mediated lysis through interaction with the inhibitory receptor CD94/NKG2A. Furthermore, iDCs infected with L. infantum up-regulate CD1d cell surface expression and consequently can be efficiently recognized and killed by iNKT cells that produce IFN-γ. These data suggest that L. infantum could be able to evade NK recognition; in contrast, iNKTs may play an important role in the immune response against Leishmania.

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Section: Endritic Cells (Dcs)mentioning

confidence: 99%

Immature Human Dendritic Cells Infected with Leishmania infantum Are Resistant to NK-Mediated Cytolysis but Are Efficiently Recognized by NKT Cells

Campos-Martín

Colmenares

Gozalbo-López

et al. 2006

The Journal of Immunology

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“…[29][30][31] and Toxoplasma gondii [32,33]. A 65 kDa heat-shock protein (HSP65) was found to be up-regulated in macrophages after infection by these organisms [34,35] and Trypanosoma cruzi [36], but its relevance to the infection remains unknown. Many viral infections, such as hepatitis C are known to confer fas ligand-specific signals on the host cells for apoptosis [37], whereas T. cruzi infection inhibits this [38].…”

Section: Introductionmentioning

confidence: 99%

Leishmania-released nucleoside diphosphate kinase prevents ATP-mediated cytolysis of macrophages

Kolli

Košťál

Zaborina

et al. 2008

Molecular and Biochemical Parasitology

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Leishmania amazonensis was found to release nucleoside diphosphate kinase (NdK) -a stable enzyme capable of decreasing extracellular ATP. The release of this enzyme from Leishmania results in its progressive accumulation extracellularly as they replicate, peaking at the stationary phase in vitro. The released NdK is immunoprecipitable and constitutes ~40% of its total activities and proteins. The retention of a known cytosolic protein by wild type cells and a fluorescent protein by DsRed transfectants at stationary phase, which release NdK, indicates that this is a spontaneous event, independent of inadvertent cytolysis. Recombinant products of Leishmania NdK prepared were enzymatically and immunologically active. Both recombinant and native Leishmania NdK utilized ATP to produce expected nucleoside triphosphates in the presence of nucleoside diphosphates in excess. Both native and recombinant Leishmania NdK were also found to prevent ATP-induced cytolysis of J774 macrophages in vitro, as determined by assays for lactate dehydrogenase release from these cells and for their mitochondrial membrane potential changes. The results obtained thus suggest that Leishmania NdK not only serves its normal house-keeping and other important functions true to all cells, but also prevents ATP-mediated lysis of macrophages, thereby preserving the integrity of the host cells to the benefit of the parasite.

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“…Studies in mice have revealed that a-GalCer treatment promotes resistance against infections, tumours and autoimmunity [15][16][17][18][19][20][21][22][23][24][25][26][27]. In a murine vaccination study, a-GalCer potentiated protective immune responses induced by malaria vaccines [28].…”

Section: Introductionmentioning

confidence: 99%

CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells

et al. 2005

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Human Va24 + Vb11 + natural killer T cells (NKT cells) are "natural memory" T cells that detect glycolipid antigens such as a-galactosylceramide (a-GalCer) presented on CD1d.In the present study we found that highly purified Va24 + NKT cells lack TLR9 mRNA, and thus are not sensitive towards stimulation with CpG oligodeoxynucleotides (ODN). Within PBMC, however, CpG ODN synergistically activated NKT cells stimulated with their cognate antigen a-GalCer. Depletion of plasmacytoid dendritic cells (PDC) or myeloid dendritic cells (MDC) revealed that both DC subsets were necessary for the synergistic activation of NKT cells by a-GalCer and CpG ODN. While PDC were responsible for the stimulation of NKT cells with CpG ODN, MDC but not PDC presented a-GalCer via CD1d. Partial activation of NKT cells was mediated by PDC-derived IFN-a, whereas full activation of NKT cells as indicated by IFN-c production required cell-tocell contact of PDC and NKT cells in addition to IFN-a; OX40 was involved in this interaction. We conclude that CpG-activated PDC enhance a-GalCer-specific NKT cell activation, and bias activated NKT cells towards a Th1 phenotype. Our results lead to a novel concept of PDC function: to regulate effector activity of antigen-stimulated T cells in a cell contact-dependent manner without the need of simultaneous presentation of the cognate T cell antigen. IntroductionNatural killer T (NKT) cells represent a small subset of non-conventional innate T cells with a restricted TCR repertoire for the recognition of glycolipid antigens presented on CD1d, an MHC class I-like molecule. NKT cells express markers of NK cells and exhibit an activated memory phenotype. Depending on the microenvironment and the type of stimulation, they can release large amounts of both Th1 and Th2 cytokines (especially IL-4 and IFN-c) and show cytotoxic activity in vitro (reviewed in [1][2][3]). In both mice and man NKT cells express a homologous semi-invariant TCR that in humans consists of a Va24 chain preferentially paired with a Vb11 chain [4]. In mice, NKT cells are most frequent in the liver (about 30% of hepatic T cells), bone marrow and thymus (reviewed in [5]). Smaller NKT cell populations are present in spleen and blood (reviewed in [5]). Similar to their murine counterparts, human NKT cells preferen-A. M., S. R. and V. H. equally contributed to this manuscript. tially accumulate in the liver though with a far lower frequency than in mice (4% of hepatic T cells) ([6, 7] and reviewed in [1,5]). Due to the conserved TCR, both mouse and human NKT cells recognise the same specific glycolipid antigen a-galactosylceramide (a-GalCer) when presented by CD1d molecules on antigen-presenting cells (APC) [8][9][10]. Originally isolated from a marine sponge, aGalCer was first described as an agent with strong antimetastatic activity in mice and later found to specifically activate NKT cells in a CD1d-restricted manner [8,11,12]. Glycolipid antigens similar to a-GalCer have been detected in certain bacteria and under some abnormal conditions...

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CD4+ Valpha14 NKT cells play a crucial role in an early stage of protective immunity against infection with Leishmania major

Cited by 103 publications

References 27 publications

Immature Human Dendritic Cells Infected with Leishmania infantum Are Resistant to NK-Mediated Cytolysis but Are Efficiently Recognized by NKT Cells

Immature Human Dendritic Cells Infected with Leishmania infantum Are Resistant to NK-Mediated Cytolysis but Are Efficiently Recognized by NKT Cells

Leishmania-released nucleoside diphosphate kinase prevents ATP-mediated cytolysis of macrophages

CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells

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