Latency-Associated Protein Acr1 Impairs Dendritic Cell Maturation and Functionality: A Possible Mechanism of Immune Evasion by Mycobacterium tuberculosis

Siddiqui, Kaneez F.; Amir, Mohammed; Gurram, Rama Krishna; Khan, Nargis; Arora, Ashish; Rajagopal, Kammara; Agrewala, Javed N.

doi:10.1093/infdis/jit595

Cited by 40 publications

(37 citation statements)

References 50 publications

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“…Thus, mycobacterial α-crystallin antigen (Acr1), which is expressed by M. tuberculosis during latency, enhances M. tuberculosis survival intracellularly and signals for a tolerogenic phenotype in cultured DCs [467]. This tolerogenic phenotype was associated with alteration of PD-L1, IDO1 and IL-10 expression, although these factors were not specifically inhibited to confirm the relative extent of their involvement [467].…”

Section: Micro-organism Induction Of Ido1 In Vivomentioning

confidence: 99%

Role of indoleamine 2,3-dioxygenase in health and disease

et al. 2015

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IDO1 (indoleamine 2,3-dioxygenase 1) is a member of a unique class of mammalian haem dioxygenases that catalyse the oxidative catabolism of the least-abundant essential amino acid, L-Trp (L-tryptophan), along the kynurenine pathway. Significant increases in knowledge have been recently gained with respect to understanding the fundamental biochemistry of IDO1 including its catalytic reaction mechanism, the scope of enzyme reactions it catalyses, the biochemical mechanisms controlling IDO1 expression and enzyme activity, and the discovery of enzyme inhibitors. Major advances in understanding the roles of IDO1 in physiology and disease have also been realised. IDO1 is recognised as a prominent immune regulatory enzyme capable of modulating immune cell activation status and phenotype via several molecular mechanisms including enzyme-dependent deprivation of L-Trp and its conversion into the aryl hydrocarbon receptor ligand kynurenine and other bioactive kynurenine pathway metabolites, or non-enzymatic cell signalling actions involving tyrosine phosphorylation of IDO1. Through these different modes of biochemical signalling, IDO1 regulates certain physiological functions (e.g. pregnancy) and modulates the pathogenesis and severity of diverse conditions including chronic inflammation, infectious disease, allergic and autoimmune disorders, transplantation, neuropathology and cancer. In the present review, we detail the current understanding of IDO1's catalytic actions and the biochemical mechanisms regulating IDO1 expression and activity. We also discuss the biological functions of IDO1 with a focus on the enzyme's immune-modulatory function, its medical implications in diverse pathological settings and its utility as a therapeutic target.

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Section: Micro-organism Induction Of Ido1 In Vivomentioning

confidence: 99%

Role of indoleamine 2,3-dioxygenase in health and disease

et al. 2015

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“…All the recombinant antigens, Acr-1 (heat shock protein hspX or 16 kDa or Rv2031c), CFP-10, ESAT-6 and PhoP were same, as used in the previous studies [13, 17]. …”

Section: Methodsmentioning

confidence: 99%

“…Therefore, they are the major reservoir of the bacterium and possible threat of spreading TB. Alpha crystalline protein (Acr-1) is a 16 kDa Ag of Mtb that is predominantly expressed in the latent phase of infection[13]. PhoP is a part of PhoPR two-component system of Mtb and regulates key functions required for virulence and intracellular survival and persistence of Mtb [14].…”

Section: Introductionmentioning

confidence: 99%

Antibody response against PhoP efficiently discriminates among healthy individuals, tuberculosis patients and their contacts

et al. 2017

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Tuberculosis continues to be one of the most devastating global health problem. Its diagnosis will benefit in timely initiation of the treatment, cure and therefore reduction in the transmission of the disease. Tests are available, but none can be comprehensively relied on for its diagnosis; especially in TB-endemic zones. PhoP is a key player in Mycobacterium tuberculosis virulence but nothing has been known about its role in the diagnosis of TB. We monitored the presence of anti-PhoP antibodies in the healthy, patients and their contacts. In addition, we also measured antibodies against early secretory antigens ESAT-6 and CFP-10, and latency associated antigen Acr-1 to include proteins that are associated with the different stages of disease progression. Healthy subjects showed high antibody titer against PhoP than patients and their contacts. In addition, a distinct pattern in the ratio of Acr-1/PhoP was observed among all cohorts. This study for the first time demonstrates a novel role of anti-PhoP antibodies, as a possible marker for the diagnosis of TB and therefore will contribute in the appropriate action and management of the disease.

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“…Mtb also subverts the differentiation of monocytes to DCs. DCs differentiated from Mtb-infected Mos display CD80 lo and MHCII lo phenotypes and defective function [34,36,99,100]. This indicates that Mtb selectively manipulates the bactericidal function of Mϕs but hampers the T-cell priming skill of DCs (Table 3).…”

Section: Different Strategies Adopted By Mtb To Exploit Dcs and Mϕsmentioning

confidence: 99%

“…Therefore, Mtb paralyzes the function of Mϕs and securely inhabits the inimical environment of Mϕs [33]. In addition, Mtb also hampers the differentiation of Mos to DCs [34,35]. Impaired DCs are defective in their function, which ultimately leads to elicitation of a weak T-cell response against Mtb [34,36,37].…”

Section: Introductionmentioning

confidence: 99%

Distinct Strategies Employed by Dendritic Cells and Macrophages in RestrictingMycobacterium tuberculosisInfection: Different Philosophies but Same Desire

Khan

Vidyarthi

Pahari

et al. 2015

International Reviews of Immunology

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Dendritic cells (DCs) and macrophages (Mϕs) are professional antigen-presenting cells (APCs) that can efficiently phagocytose Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB). It is quite interesting to mention here that DCs and Mϕs use distinct strategies to combat and eliminate Mtb. Similarly, Mtb employs different mechanisms to counteract the action of DCs and Mϕs. Mϕs are evolved with specialized, innate, defensive machinery to restrict growth of Mtb at the initial phase of infection. However, DCs are more endowed toward initiating adaptive immunity by activating naïve T cells. During encounter with Mtb, DCs and Mϕs deliver discrete functions via triggering through different pattern recognition receptors (PRRs) expressed by these APCs. Mtb-infected DCs and Mϕs show differential expression of genes encoding cytokines, chemokines, costimulatory molecules, and adhesion molecules. Interestingly, Mtb impairs the immune defensive machinery by exploiting various PRRs. Remarkably, selective signaling through PRRs by Mtb abrogates the bactericidal activity of Mϕs, but subverts differentiation of monocytes to DCs. In this article, we highlight the role of PRRs in inducing distinct immune response by DCs and Mϕs against Mtb. Concurrently, we also discuss smart strategies exploited by Mtb to impair the function of host DCs and Mϕs.

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Latency-Associated Protein Acr1 Impairs Dendritic Cell Maturation and Functionality: A Possible Mechanism of Immune Evasion by Mycobacterium tuberculosis

Cited by 40 publications

References 50 publications

Role of indoleamine 2,3-dioxygenase in health and disease

Role of indoleamine 2,3-dioxygenase in health and disease

Antibody response against PhoP efficiently discriminates among healthy individuals, tuberculosis patients and their contacts

Distinct Strategies Employed by Dendritic Cells and Macrophages in RestrictingMycobacterium tuberculosisInfection: Different Philosophies but Same Desire

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