Role of the polypeptide region of a 33kDa mycobacterial lipoprotein for efficient IL-12 production

Yamashita, Yasuko; Maeda, Yosuke; Takeshita, Fumihiko; Brennan, Patrick J.; Makino, Masahiko

doi:10.1016/j.cellimm.2004.06.001

Cited by 7 publications

(7 citation statements)

References 27 publications

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“…Synthetic lipopeptides representing the 19-kDa and 33-kDa lipoproteins activated both monocytes and dendritic cells (DCs). Additional studies demonstrated that the M. leprae 33-kDa lipoprotein [17] and the M. leprae major membrane protein-II (MMP-II) [18], also a lipoprotein, triggered TLR2 responses, requiring the acyl functions and the polypeptide region for optimal activity. Activation was enhanced by type 1 cytokines and inhibited by type 2 cytokines.…”

Section: Toll-like Receptor 2/1 (Tlr2/1)mentioning

confidence: 99%

The innate immune response in leprosy

Modlin¹

2010

Current Opinion in Immunology

104

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Investigation into the innate immune response in leprosy has provided insight into immunoregulation in human infectious disease. Key advances include the role of pattern recognition receptors in recognizing pathogen-associated molecular patterns of Mycobacterium leprae, cytokine release by innate immune cells, macrophage and dendritic cell differentiation, as well as antimicrobial effector pathways. These insights provide targets for therapeutic intervention in modulating the course of leprosy and other chronic infectious diseases.

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Section: Toll-like Receptor 2/1 (Tlr2/1)mentioning

confidence: 99%

The innate immune response in leprosy

Modlin¹

2010

Current Opinion in Immunology

104

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“…For example, the mechanisms by which non-acylated ligands, such as neisserial porins [18] and capsular carbohydrates [19], are recognized by TLR2 and its co-receptors remain unclear. For full-length, natural lipoproteins, it remains unknown how the peptide component [20] or glycan component [21] may influence signaling by TLR2, TLR1 and TLR6. Our studies used co-receptor knock-out cells to assess TLR2 co-receptor requirements for responses to four different Mtb lipoproteins, revealing variable dependence on TLR1 and a lack of dependence on TLR6.…”

Section: Introductionmentioning

confidence: 99%

TLR2 and its co-receptors determine responses of macrophages and dendritic cells to lipoproteins of Mycobacterium tuberculosis

Drage

Pecora

Hise

et al. 2009

Cellular Immunology

144

119

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Mycobacterium tuberculosis (Mtb) signals through Toll-like receptor 2 (TLR2) to regulate antigen presenting cells (APCs). Mtb lipoproteins, including LpqH, LprA, LprG and PhoS1, are TLR2 agonists, but their co-receptor requirements are unknown. We studied Mtb lipoprotein-induced responses in TLR2−/−, TLR1−/−, TLR6−/−, CD14−/− and CD36−/− macrophages. Responses to LprA, LprG, LpqH and PhoS1 were completely dependent on TLR2. LprG, LpqH, and PhoS1 were dependent on TLR1, but LprA did not require TLR1. None of the lipoproteins required TLR6, although a redundant contribution by TLR6 cannot be excluded. CD14 contributed to detection of LprA, LprG and LpqH, whereas CD36 contributed only to detection of LprA. Studies of lung APC subsets revealed lower TLR2 expression by CD11bhigh/CD11clow lung macrophages than CD11blow/CD11chigh alveolar macrophages, which correlated with hyporesponsiveness of lung macrophages to LpqH. Thus, lung APC subsets differ in TLR expression, which may determine differences in responses to Mtb.

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“…Truncated protein, having the N-terminal 60 amino acids of 33-kD lipoprotein, had cytokine inducing ability in human monocytes, in contrast to the C-terminal 192 amino acids having no such ability [5]. In this study, we synthesized the lipopeptide (LipoK) having the N-terminal 13 amino acids of the 33-kD M. leprae lipoprotein linked to tri-palmitoylated portion of a lipid.…”

Section: Introductionmentioning

confidence: 99%

A Lipopeptide Facilitate Induction of Mycobacterium leprae Killing in Host Cells

et al. 2011

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Little is known of the direct microbicidal activity of T cells in leprosy, so a lipopeptide consisting of the N-terminal 13 amino acids lipopeptide (LipoK) of a 33-kD lipoprotein of Mycobacterium leprae, was synthesized. LipoK activated M. leprae infected human dendritic cells (DCs) to induce the production of IL-12. These activated DCs stimulated autologous CD4+ or CD8+ T cells towards type 1 immune response by inducing interferon-gamma secretion. T cell proliferation was also evident from the CFSE labeling of target CD4+ or CD8+ T cells. The direct microbicidal activity of T cells in the control of M. leprae multiplication is not well understood. The present study showed significant production of granulysin, granzyme B and perforin from these activated CD4+ and CD8+ T cells when stimulated with LipoK activated, M. leprae infected DCs. Assessment of the viability of M. leprae in DCs indicated LipoK mediated T cell-dependent killing of M. leprae. Remarkably, granulysin as well as granzyme B could directly kill M. leprae in vitro. Our results provide evidence that LipoK could facilitate M. leprae killing through the production of effector molecules granulysin and granzyme B in T cells.

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Role of the polypeptide region of a 33kDa mycobacterial lipoprotein for efficient IL-12 production

Cited by 7 publications

References 27 publications

The innate immune response in leprosy

The innate immune response in leprosy

TLR2 and its co-receptors determine responses of macrophages and dendritic cells to lipoproteins of Mycobacterium tuberculosis

A Lipopeptide Facilitate Induction of Mycobacterium leprae Killing in Host Cells

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