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.
"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. "
"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). "
[Show abstract][Hide abstract] ABSTRACT: Studies over the past decade have helped to decipher molecular networks dependent on Toll-like receptor (TLR) signaling, in mycobacteria-infected macrophages. Stimulation of TLRs by mycobacteria and their antigenic components rapidly induces intracellular signaling cascades involved in the activation of nuclear factor-κB and mitogen-activated protein kinase pathways, which play important roles in orchestrating proinflammatory responses and innate defense through generation of a variety of antimicrobial effector molecules. Recent studies have provided evidence that mycobacterial TLR-signaling cross talks with other intracellular antimicrobial innate pathways, the autophagy process and functional vitamin D receptor (VDR) signaling. In this article we describe recent advances in the recognition, responses, and regulation of mycobacterial signaling through TLRs.
Frontiers in Cellular and Infection Microbiology 11/2012; 2:145. DOI:10.3389/fcimb.2012.00145 · 3.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is one of the world's leading infectious causes of morbidity and mortality. As a mucosal-transmitted pathogen, Mtb infects humans and animals mainly through the mucosal tissue of the respiratory tract. Apart from providing a physical barrier against the invasion of pathogen, the major function of the respiratory mucosa may be to serve as the inductive sites to initiate mucosal immune responses and sequentially provide the first line of defense for the host to defend against this pathogen. A large body of studies in the animals and humans have demonstrated that the mucosal immune system, rather than the systemic immune system, plays fundamental roles in the host's defense against Mtb infection. Therefore, the development of new vaccines and novel delivery routes capable of directly inducing respiratory mucosal immunity is emphasized for achieving enhanced protection from Mtb infection. In this paper, we outline the current state of knowledge regarding the mucosal immunity against Mtb infection, including the development of TB vaccines, and respiratory delivery routes to enhance mucosal immunity are discussed.
N Mørk, E Kofod-Olsen, K B Sørensen, E Bach, T F Ørntoft, L Østergaard, S R Paludan, M Christiansen, T H Mogensen
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