Abstract
BackgroundMycobacterium 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.ResultsHere 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.ConclusionTogether our data indicate that 30-kDa and 38-kDa Mtb antigens induced only partial DC maturation shifting immune responses towards a Th2 profile.
Highlights
Mycobacterium tuberculosis (Mtb) infections are still a major cause of death among all infectious diseases
Modified BCG vaccines are the most common tested in clinical trials and few selective Mtb antigens have been tested for their capacity to stimulate immune responses in order to use them as a vaccine [3]
Here we showed that the 30-kDa and 38-kDa antigens as Mtb components induce only a partial dendritic cell (DC) maturation leading to a Th2 shift in T cell polarization assays
Summary
Mycobacterium tuberculosis (Mtb) infections are still a major cause of death among all infectious diseases. 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. BCG as an attenuated strain of M. bovis has been used as a vaccine against Mtb. Currently modified BCG vaccines are the most common tested in clinical trials and few selective Mtb antigens have been tested for their capacity to stimulate immune responses in order to use them as a vaccine [3]. Immune deviation towards Th2 responses is a hallmark of many infections leading to microbial persistence [4]. We wanted to investigate whether immune deviation could be detected by selective Mtb components. We studied these factors not as antigens presented on MHC molecules but as factors to induce DC maturation. The quality of DC maturation was assessed as well as the DC-mediated immune responses of CD4+ T cells
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