BCG stimulated dendritic cells induce an interleukin‐10 producing T‐cell population with no T helper 1 or T helper 2 bias <i>in vitro</i>

Larsen, Jeppe Madura; Benn, Christine Stabell; Fillié, Yvonne E.; Kleij, Desirée van der; Aaby, Péter; Yazdanbakhsh, Maria

doi:10.1111/j.1365-2567.2007.02575.x

Cited by 61 publications

(38 citation statements)

References 38 publications

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“…In fact unvaccinated children at 4 1/2 mo of age had greater levels of IL-10 in BCG cultures than the BCG vaccinated individuals, suggesting that mycobacterial induced IL-10 could play a role in attenuating induction of the protective mycobacterial response after BCG vaccination. A lack of IL-10 upregulation after BCG vaccination is in conflict with other studies (46,47,58). A South African study showed upregulation of IL-10, albeit at very low levels (,0.01% of CD4 + or CD8 + T cells) in 12 h BCG cultures (47).…”

Section: Discussioncontrasting

confidence: 51%

Delaying Bacillus Calmette-Guérin Vaccination from Birth to 4 1/2 Months of Age Reduces Postvaccination Th1 and IL-17 Responses but Leads to Comparable Mycobacterial Responses at 9 Months of Age

Burl

Adetifa

Cox

et al. 2010

The Journal of Immunology

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Bacillus Camette-Guérin (BCG) vaccine is the only licensed vaccine against tuberculosis, yet its protective efficacy is highly variable between different geographical regions. We hypothesized that exposure to nontuberculous mycobacteria attenuates BCG immunogenicity by inducing mycobacterial-specific regulatory T cells (Tregs). Gambian neonates were recruited at birth and randomized to receive BCG vaccination either at birth or at 4 1/2 mo. Mycobacterial immune responses were assessed at birth, 4 1/2, and 9 mo of age. At 4 1/2 mo of age the BCG naive individuals had detectable mycobacterial responses, including increased IL-10 production suggesting environmental priming. Vaccination at birth significantly enhanced Th1, Th2, IL-6, IL-17, and Treg responses in mycobacterial cultures at 4 1/2 mo compared with the BCG naive group. Analyzing results at 4 1/2 mo postvaccination revealed lower IFN-γ, IL-6, and IL-17 responses in the delayed BCG vaccine group compared with those vaccinated at birth, but this did not relate to Treg levels prevaccination. When comparing responses pre- and post-BCG vaccination in the delayed vaccine group, there was no priming of mycobacterial IL-17. Mycobacterial responses waned over 9 mo in those vaccinated at birth, leading to comparable mycobacterial immunity in both groups at 9 mo of age. Overall, these data suggest that vaccination at birth induces a broad Th1/Th2/IL-17/Treg mycobacterial response but the Th1/Th-17 response was reduced when delaying the vaccine. The evidence did not suggest that mycobacterial specific naturally occurring Tregs accounted for this attenuated immunogenicity.

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Section: Discussioncontrasting

confidence: 51%

Delaying Bacillus Calmette-Guérin Vaccination from Birth to 4 1/2 Months of Age Reduces Postvaccination Th1 and IL-17 Responses but Leads to Comparable Mycobacterial Responses at 9 Months of Age

Burl

Adetifa

Cox

et al. 2010

The Journal of Immunology

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“…Signaling between cells may aid these responses because lymphocytes produce IL-10 in response to various bacteria such as Mycobacteria spp. (75,76) and Helicobacter spp. (77), and intercellular interactions can be essential to drive antibacterial responses (78).…”

Section: Discussionmentioning

confidence: 99%

Innate Transcriptional Networks Activated in Bladder in Response to Uropathogenic Escherichia coli Drive Diverse Biological Pathways and Rapid Synthesis of IL-10 for Defense against Bacterial Urinary Tract Infection

Duell

Carey

Tan

et al. 2012

The Journal of Immunology

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Early transcriptional activation events that occur in bladder immediately following bacterial urinary tract infection (UTI) are not well defined. In this study, we describe the whole bladder transcriptome of uropathogenic Escherichia coli (UPEC) cystitis in mice using genome-wide expression profiling to define the transcriptome of innate immune activation stemming from UPEC colonization of the bladder. Bladder RNA from female C57BL/6 mice, analyzed using 1.0 ST-Affymetrix microarrays, revealed extensive activation of diverse sets of innate immune response genes, including those that encode multiple IL-family members, receptors, metabolic regulators, MAPK activators, and lymphocyte signaling molecules. These were among 1564 genes differentially regulated at 2 h postinfection, highlighting a rapid and broad innate immune response to bladder colonization. Integrative systems-level analyses using InnateDB (http://www.innatedb.com) bioinformatics and ingenuity pathway analysis identified multiple distinct biological pathways in the bladder transcriptome with extensive involvement of lymphocyte signaling, cell cycle alterations, cytoskeletal, and metabolic changes. A key regulator of IL activity identified in the transcriptome was IL-10, which was analyzed functionally to reveal marked exacerbation of cystitis in IL-10–deficient mice. Studies of clinical UTI revealed significantly elevated urinary IL-10 in patients with UPEC cystitis, indicating a role for IL-10 in the innate response to human UTI. The whole bladder transcriptome presented in this work provides new insight into the diversity of innate factors that determine UTI on a genome-wide scale and will be valuable for further data mining. Identification of protective roles for other elements in the transcriptome will provide critical new insight into the complex cascade of events that underpin UTI.

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“…Importantly, mycobacteria, including the vaccine strain M. bovis bacillus Calmette-Guérin (BCG), are able to suppress the immune response by interfering with the normal function of DCs (23,73). Induction of the immunosuppressive cytokine interleukin-10 (IL-10) has a negative effect on the production of the proinflammatory cytokine IL-12 and inhibits a Th1-biased response which is necessary for mycobacterial clearance (14,45). Responsible for at least part of this immune modulation is the binding of mycobacteria to the C-type lectin DCspecific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN [CD209]) (26,69).…”

mentioning

confidence: 99%

Role of Phosphatidylinositol Mannosides in the Interaction between Mycobacteria and DC-SIGN

et al. 2009

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The C-type lectin dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is the major receptor on DCs for mycobacteria of the Mycobacterium tuberculosis complex. Recently, we have shown that although the mannose caps of the mycobacterial surface glycolipid lipoarabinomannan (ManLAM) are essential for the binding to DC-SIGN, genetic removal of these caps did not diminish the interaction of whole mycobacteria with DC-SIGN and DCs. Here we investigated the role of the structurally related glycolipids phosphatidylinositol mannosides (PIMs) as possible ligands for DC-SIGN. In a binding assay with both synthetic and natural PIMs, DC-SIGN exhibited a high affinity for hexamannosylated PIM 6 , which contains terminal ␣(132)-linked mannosyl residues identical to the mannose cap on ManLAM, but not for di-and tetramannosylated PIM 2 and PIM 4 , respectively. To determine the role of PIM 6 in the binding of whole mycobacteria to DC-SIGN, a mutant strain of M. bovis bacillus Calmette-Guérin deficient in the production of PIM 6 (⌬pimE) was created, as well as a double knockout deficient in the production of both PIM 6 and the mannose caps on LAM (⌬pimE ⌬capA). Compared to the wild-type strain, both mutant strains bound similarly well to DC-SIGN and DCs. Furthermore, the wild-type and mutant strains induced comparable levels of interleukin-10 and interleukin-12p40 when used to stimulate DCs. Hence, we conclude that, like ManLAM, PIM 6 represents a bona fide DC-SIGN ligand but that other, as-yet-unknown, ligands dominate in the interaction between mycobacteria and DCs.

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BCG stimulated dendritic cells induce an interleukin‐10 producing T‐cell population with no T helper 1 or T helper 2 bias in vitro

Cited by 61 publications

References 38 publications

Delaying Bacillus Calmette-Guérin Vaccination from Birth to 4 1/2 Months of Age Reduces Postvaccination Th1 and IL-17 Responses but Leads to Comparable Mycobacterial Responses at 9 Months of Age

Delaying Bacillus Calmette-Guérin Vaccination from Birth to 4 1/2 Months of Age Reduces Postvaccination Th1 and IL-17 Responses but Leads to Comparable Mycobacterial Responses at 9 Months of Age

Innate Transcriptional Networks Activated in Bladder in Response to Uropathogenic Escherichia coli Drive Diverse Biological Pathways and Rapid Synthesis of IL-10 for Defense against Bacterial Urinary Tract Infection

Role of Phosphatidylinositol Mannosides in the Interaction between Mycobacteria and DC-SIGN

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