Mycobacterium tuberculosis lpdC, Rv0462, induces dendritic cell maturation and Th1 polarization

Department of Microbiology and Immunology, School of Medicine, Pusan National University, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770, South Korea.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 08/2011; 411(3):642-7. DOI: 10.1016/j.bbrc.2011.07.013
Source: PubMed


Mycobacterium tuberculosis, the etiological factor of pulmonary tuberculosis, causes significant morbidity and mortality worldwide. Activation of host immune responses for containment of mycobacterial infections involves participation of innate immune cells, such as dendritic cells (DCs). In this study, we demonstrated that the gene encoding lipoamide dehydrogenase C (lpdC) from M. tuberculosis, Rv0462, induce maturation and activation of DCs involved in the MAPKs signaling pathway. Moreover, Rv0462-treated DCs activated naïve T cells, polarized CD4(+) and CD8(+) T cells to secrete IFN-γ in syngeneic mixed lymphocyte reactions, which would be expected to contribute to Th1 polarization of the immune response. Our results suggest that Rv0462 can contribute to the innate and adaptive immune responses during tuberculosis infection, and thus modulate the clinical course of tuberculosis.

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    • "Meanwhile, PEPCK is essential for virulence of M. bovis, when deleting PEPCKencoding gene pckA, the capacity of the bacteria to infect and survive in macrophages is reduced [Liu et al., 2003]. Fuethermore, dihydrolipoamide dehydrogenase, a member of pyruvate dehydrogenase complex, can control virulence in M. tuberculosis, inducing dendritic cell maturation and Th1 polarization [Heo et al., 2011; Venugopal et al., 2011]. This implies that acetylation might play a role in the pathogenesis of these M. tuberculosis key regulators. "
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    • "Many previous studies have reported that mycobacterial components are involved in innate recognition and responses through TLR signaling (Basu et al., 2007; Pathak et al., 2009; Bansal et al., 2010, 2011; Heo et al., 2011; Byun et al., 2012a,b). Antigens of the PE_PGRS family, namely, PE_PGRS 17 (Rv0978c) and PE_PGRS 11 (Rv0754), recognize TLR2 to induce maturation and activation of human dendritic cells, and enhance the ability of dendritic cells to stimulate CD4(+) T cells (Bansal et al., 2010). "
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