Vaccine Potential of Mycobacterium Tuberculosis ‘PE Only’ Subfamily Antigens

Opinion

The M. tuberculosis activates the alveolar macrophages, which leads to activate and recruiter the other immune cells including T cells and B cells, as well as induce the immune response against the pathogens [3]. The continuous research and investigation of immunopathogenesis of TB suggested that the “PE only” subfamily” antigens of M. tuberculosis are capable to induce the protective immune response in the host to reduce the replication or eliminate of bacilli form the host. The “PE only” subfamily” antigens named because of contains a conserved Pro-Glu (PE) motif at the N-terminal of 90-110 amino acids length [5]. This antigen family are exclusively present in the pathogenic strain of mycobacteria. PE antigens exhibit several repetitive sequences and abundance of immunogenic regions, which represent a source of T cell and B cell epitopes [6]. The highly immunogenic nature of PE subfamily antigens has been demonstrated by epitope mapping to show the considerable degree of cross-reactivity of these antigens in the elicited T cells [7, 8], and generation of IFN-γ induced T cell responses during infection. The PE18 and PE19 proteins are rich of CD4+-specific epitopes, which significantly induce the cell-mediated immune response [9]. The mice infected with PE4 antigen, detected the higher secretion of pro-inflammatory cytokines, including IL-2, TNF, and IL-6, which capable to induce the protective immunity in mice against M. tuberculosis challenge [10]. PE13 increase the expression of IL-6 and IL-1β and decreased SOCS3 expression in macrophages [11].

PE27 functionally and phenotypically induces the maturation of dendritic cells, by increasing the expression of MHC class I, MHC class II, CD80 and CD86 on the surface of dendritic cells to induce the production of IL-1β, IL-6, IL-12p70 and TNF-α, via NF- κB and MAPK signaling pathways. The PE27-induced dendritic cells regulate the naïve CD4+T cells to increase the secretion of IFN-γ. In M. tuberculosis-infected mice, PE27 activates the memory T cell to induce the production of IFN-γ, indicating the contribution of this antigen in Th1-polarization [12]. These finding suggested that PE27 induced DC maturation and Th1-polarizing could be helpful to design the vaccine against TB [12]. The mice immunize with PE3 protein, can significantly induce the secretion of pro-inflammatory cytokines such as IL-2, IL-6 and TNF and induce the strong protective immune response against mice challenged with live mycobacteria, could be a prospective subunit vaccine candidate against TB [13]. The PE35 and PPE68 recombinant, single or combined, stimulated THP-1 macrophages induce the dose-dependent secretion of anti-inflammatory cytokine IL-10 and chemokine monocyte chemoattractant protein-1, as well as reduce the secretion of pro-inflammatory cytokine IL-12 [14].

Conclusion

The PE32/PPE65 protein complex reduces the secretion of pro-inflammatory cytokines IL-6 and TNF-α, while induce the secretion of anti-inflammatory cytokine IL-10 in the macrophages. Co-transcription and co-translation of PE32 and PPE65 antigens modulates the protective host immune response against mycobacteria, by impeding the Th1 cells response [15]. The PE9- PE10 protein complex interact with TLR4 in the macrophages, leads to increase the phospho-IRF-3 level, which associate with the inducing transcription level of its target gene IL-1β. The PE9-PE10 protein complex stimulated macrophages induce the transcription level of IL-10, while reduce the transcription level of IL-1β (Tiwari et al. 2015). The Δppe25-pe19 mutant strain is capable to secrete the ESX-1 substrates, which leads to evoke the CD4+ T-cell responses against these protective immunogens [16]. Research so far revealed that PE only” subfamily antigens are capable to influence the host cellular immunity by modulating the macrophages, T lymphocytes, B lymphocytes, and cytokines profile, which contribute to the protective immune responses against M. tuberculosis-induced disease (Figure 1). In my opinion, “PE only” subfamily antigens could be considerable candidates having good potential to develop the powerful peptide vaccine against TB.

Figure 1: PE sub-family” antigen induced protective immune response. PE sub-family” antigens bind with the APC (antigen presenting cells) and activate the immune cells, which induce the protective immune response against M. tuberculosis.

References

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