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Open Access Research article

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

Marion Heuer1, Anna-Sophie Behlich1, Ji-Sook Lee2, Eliana Ribechini1, Eun-Kyeong Jo2 and Manfred B Lutz1*

Author Affiliations

1 Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany

2 Department of Microbiology, College of Medicine, Konyang University, Daejeon 302-718, South Korea

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BMC Immunology 2013, 14:48  doi:10.1186/1471-2172-14-48

Published: 3 October 2013

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.

Keywords:
Dendritic cells; Mycobacterium tuberculosis; T helper cell responses