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The 30-kDa and 38-kDa antigens from Mycobacterium tuberculosis induce partial maturation of human dendritic cells shifting CD4(+) T cell responses towards IL-4 production.

Heuer M, Behlich AS, Lee JS, Ribechini E, Jo EK, Lutz MB - BMC Immunol. (2013)

Bottom Line: DC maturation markers CD80, CD86 and CD83 were readily upregulated by H37Ra- and H37Rv-associated antigens, the 30-kDa (from Ag85 B complex) and 38-KDa Mtb antigens only partially induced these markers.Although the proliferation levels of primary T cell responses were comparable using all the differentially stimulated DC, the 30-kDa and 38-kDa antigens showed a bias towards IL-4 secretion of polarized CD4(+) T cells after secondary stimulation as compared to H37Ra and H37Rv preparations.Together our data indicate that 30-kDa and 38-kDa Mtb antigens induced only partial DC maturation shifting immune responses towards a Th2 profile.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany. m.lutz@vim.uni-wuerzburg.de.

ABSTRACT

Background: Mycobacterium tuberculosis (Mtb) infections are still a major cause of death among all infectious diseases. Although 99% of individuals infected with Mtb develop a CD4(+) Th1 and CD8(+) T cell mediated immunity as measured by tuberculin skin test, this results only in partial protection and Mtb vaccines are not effective. Deviation of immune responses by pathogens towards a Th2 profile is a common mechanism of immune evasion, typically leading to the persistence of the microbes.

Results: Here we tested the stimulatory capacity of selective Mtb antigens on human monocyte-derived dendritic cell (DC) maturation and cytokine production. DC maturation markers CD80, CD86 and CD83 were readily upregulated by H37Ra- and H37Rv-associated antigens, the 30-kDa (from Ag85 B complex) and 38-KDa Mtb antigens only partially induced these markers. All Mtb antigens induced variable levels of IL-6 and low levels of IL-10, there was no release of IL-12p70 detectable. Substantial IL-12p40 production was restricted to LPS or H37Ra and H37Rv preparations. Although the proliferation levels of primary T cell responses were comparable using all the differentially stimulated DC, the 30-kDa and 38-kDa antigens showed a bias towards IL-4 secretion of polarized CD4(+) T cells after secondary stimulation as compared to H37Ra and H37Rv preparations.

Conclusion: Together our data indicate that 30-kDa and 38-kDa Mtb antigens induced only partial DC maturation shifting immune responses towards a Th2 profile.

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Related in: MedlinePlus

DCs show only a partial maturation on 30-kDa and 38-kDa Mtb antigen stimulation. DCs were generated from peripheral blood monocytes of healthy donors and at day 5 of culture stimulated with 10 μg of the indicated Mtb antigens or LPS or left untreated in buffer as a control for 24 h. Then cells were stained at the cell surface for the indicated markers (dotted or straight lines). Gray histograms show the markers on immature DC (control). The experiment is representative of 5 independent experiments.
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Figure 1: DCs show only a partial maturation on 30-kDa and 38-kDa Mtb antigen stimulation. DCs were generated from peripheral blood monocytes of healthy donors and at day 5 of culture stimulated with 10 μg of the indicated Mtb antigens or LPS or left untreated in buffer as a control for 24 h. Then cells were stained at the cell surface for the indicated markers (dotted or straight lines). Gray histograms show the markers on immature DC (control). The experiment is representative of 5 independent experiments.

Mentions: Various mycobacterial components induce maturation of DCs but mostly Mtb surface products have been investigated [16]. The immunogenicity of the different Mtb preparations was tested by their incubation with human monocyte-derived DC in vitro. After 24 h of stimulation positive control DC that were stimulated with LPS, strongly upregulated the key surface markers CD80, CD83 and CD86 (Figure 1). The Mtb preparations H37Rv and H37Ra showed a low stimulatory capacity and the 30-kDa and 38-kDa preparations had only a weak or even no effect on these markers (Figure 1). In comparison to the strong maturation by Mtb surface products that was similar to LPS [16], only a mild upregulation of typical maturation markers was observed here.


The 30-kDa and 38-kDa antigens from Mycobacterium tuberculosis induce partial maturation of human dendritic cells shifting CD4(+) T cell responses towards IL-4 production.

Heuer M, Behlich AS, Lee JS, Ribechini E, Jo EK, Lutz MB - BMC Immunol. (2013)

DCs show only a partial maturation on 30-kDa and 38-kDa Mtb antigen stimulation. DCs were generated from peripheral blood monocytes of healthy donors and at day 5 of culture stimulated with 10 μg of the indicated Mtb antigens or LPS or left untreated in buffer as a control for 24 h. Then cells were stained at the cell surface for the indicated markers (dotted or straight lines). Gray histograms show the markers on immature DC (control). The experiment is representative of 5 independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852591&req=5

Figure 1: DCs show only a partial maturation on 30-kDa and 38-kDa Mtb antigen stimulation. DCs were generated from peripheral blood monocytes of healthy donors and at day 5 of culture stimulated with 10 μg of the indicated Mtb antigens or LPS or left untreated in buffer as a control for 24 h. Then cells were stained at the cell surface for the indicated markers (dotted or straight lines). Gray histograms show the markers on immature DC (control). The experiment is representative of 5 independent experiments.
Mentions: Various mycobacterial components induce maturation of DCs but mostly Mtb surface products have been investigated [16]. The immunogenicity of the different Mtb preparations was tested by their incubation with human monocyte-derived DC in vitro. After 24 h of stimulation positive control DC that were stimulated with LPS, strongly upregulated the key surface markers CD80, CD83 and CD86 (Figure 1). The Mtb preparations H37Rv and H37Ra showed a low stimulatory capacity and the 30-kDa and 38-kDa preparations had only a weak or even no effect on these markers (Figure 1). In comparison to the strong maturation by Mtb surface products that was similar to LPS [16], only a mild upregulation of typical maturation markers was observed here.

Bottom Line: DC maturation markers CD80, CD86 and CD83 were readily upregulated by H37Ra- and H37Rv-associated antigens, the 30-kDa (from Ag85 B complex) and 38-KDa Mtb antigens only partially induced these markers.Although the proliferation levels of primary T cell responses were comparable using all the differentially stimulated DC, the 30-kDa and 38-kDa antigens showed a bias towards IL-4 secretion of polarized CD4(+) T cells after secondary stimulation as compared to H37Ra and H37Rv preparations.Together our data indicate that 30-kDa and 38-kDa Mtb antigens induced only partial DC maturation shifting immune responses towards a Th2 profile.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany. m.lutz@vim.uni-wuerzburg.de.

ABSTRACT

Background: Mycobacterium tuberculosis (Mtb) infections are still a major cause of death among all infectious diseases. Although 99% of individuals infected with Mtb develop a CD4(+) Th1 and CD8(+) T cell mediated immunity as measured by tuberculin skin test, this results only in partial protection and Mtb vaccines are not effective. Deviation of immune responses by pathogens towards a Th2 profile is a common mechanism of immune evasion, typically leading to the persistence of the microbes.

Results: Here we tested the stimulatory capacity of selective Mtb antigens on human monocyte-derived dendritic cell (DC) maturation and cytokine production. DC maturation markers CD80, CD86 and CD83 were readily upregulated by H37Ra- and H37Rv-associated antigens, the 30-kDa (from Ag85 B complex) and 38-KDa Mtb antigens only partially induced these markers. All Mtb antigens induced variable levels of IL-6 and low levels of IL-10, there was no release of IL-12p70 detectable. Substantial IL-12p40 production was restricted to LPS or H37Ra and H37Rv preparations. Although the proliferation levels of primary T cell responses were comparable using all the differentially stimulated DC, the 30-kDa and 38-kDa antigens showed a bias towards IL-4 secretion of polarized CD4(+) T cells after secondary stimulation as compared to H37Ra and H37Rv preparations.

Conclusion: Together our data indicate that 30-kDa and 38-kDa Mtb antigens induced only partial DC maturation shifting immune responses towards a Th2 profile.

Show MeSH
Related in: MedlinePlus