Evasion and subversion of antigen presentation by <i>Mycobacterium tuberculosis</i>

Baena, Andrés; Porcelli, Steven A.

doi:10.1111/j.1399-0039.2009.01301.x

Cited by 131 publications

(121 citation statements)

References 145 publications

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“…It is well known that one of the mechanisms developed by M. tuberculosis to elude the immune system is by interfering with MHC class II molecule expression and with the activation of infected APC (11). Interestingly, D-Mtb caused a reduction of the MHC class II molecule expression on APC, but the extent of reduction was comparable to that caused by R-Mtb (Fig.…”

Section: D-mtb and R-mtb Similarly Activate Human Apcmentioning

confidence: 83%

“…Even though the physical location of bacilli during LTBI remains poorly understood (9, 49, 50), it is conceivable that dormant bacteria reside in cells, which have a scarce ability to act as APC, but behave as an M. tuberculosis reservoir instead. It may be thought that R-Mtb shifts to dormancy within infected macrophages after having subverted their antimicrobial and APC potential (11). Additionally, M. tuberculosis may reside within subverted or foamy macrophages in mature granulomas (51,52), where T cells are physically separated from infected cells by a fibrous wall or caseum that limits APC/lymphocyte interactions (4).…”

Section: Discussionmentioning

confidence: 99%

“…In active disease, M. tuberculosis mainly infects professional phagocytes in the lungs where it uses strategies such as prevention of phagolysosome maturation, subversion of host cell death pathways, and the immune system to survive and replicate (11,12). In LTBI, M. tuberculosis is thought to survive in a dormant, nonreplicating form supposedly confined in storage cells in lung and other organs (13,14) of asymptomatic individuals, where it may persist for years.…”

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confidence: 99%

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Dormant Mycobacterium tuberculosis Fails To Block Phagosome Maturation and Shows Unexpected Capacity To Stimulate Specific Human T Lymphocytes

Mariotti

Pardini

Gagliardi

et al. 2013

The Journal of Immunology

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Dormancy is defined as a stable but reversible nonreplicating state of Mycobacterium tuberculosis. It is currently thought that dormant M. tuberculosis (D-Mtb) is responsible for latent tuberculosis (TB) infection. Recently, D-Mtb was also shown in sputa of patients with active TB, but the capacity of D-Mtb to stimulate specific immune responses was not investigated. We observed that purified protein derivative–specific human CD4+ T lymphocytes recognize mycobacterial Ags more efficiently when macrophages are infected with D-Mtb instead of replicating M. tuberculosis (R-Mtb). The different Ag recognition occurs even when the two forms of mycobacteria equally infect and stimulate macrophages, which secrete the same cytokine pattern and express MHC class I and II molecules at the same levels. However, D-Mtb but not R-Mtb colocalizes with mature phagolysosome marker LAMP-1 and with vacuolar proton ATPase in macrophages. D-Mtb, unlike R-Mtb, is unable to interfere with phagosome pH and does not inhibit the proteolytic efficiency of macrophages. We show that D-Mtb downmodulates the gene Rv3875 encoding for ESAT-6, which is required by R-Mtb to block phagosome maturation together with Rv3310 gene product SapM, previously shown to be downregulated in D-Mtb. Thus, our results indicate that D-Mtb cannot escape MHC class II Ag-processing pathway because it lacks the expression of genes required to block the phagosome maturation. Data suggest that switching to dormancy not only represents a mechanism of survival in latent TB infection, but also a M. tuberculosis strategy to modulate the immune response in different stages of TB.

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Section: D-mtb and R-mtb Similarly Activate Human Apcmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Dormant Mycobacterium tuberculosis Fails To Block Phagosome Maturation and Shows Unexpected Capacity To Stimulate Specific Human T Lymphocytes

Mariotti

Pardini

Gagliardi

et al. 2013

The Journal of Immunology

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“…This hyperconservation suggests that these epitopes may act as decoys, diverting the immune response from recognizing more relevant MTB proteins and thereby favoring MTB persistence (4). However, the immunological consequence of the conservation of MTB sequences across other species of the Mycobacteria genus has received less attention at the level of the specific epitopes.…”

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confidence: 99%

Immunological consequences of intragenus conservation ofMycobacterium tuberculosisT-cell epitopes

Arlehamn

Paul

Mele

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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A previous unbiased genome-wide analysis of CD4 Mycobacterium tuberculosis (MTB) recognition using peripheral blood mononuclear cells from individuals with latent MTB infection (LTBI) or nonexposed healthy controls (HCs) revealed that certain MTB sequences were unexpectedly recognized by HCs. In the present study, it was found that, based on their pattern of reactivity, epitopes could be divided into LTBI-specific, mixed reactivity, and HC-specific categories. This pattern corresponded to sequence conservation in nontuberculous mycobacteria (NTMs), suggesting environmental exposure as an underlying cause of differential reactivity. LTBI-specific epitopes were found to be hyperconserved, as previously reported, whereas the opposite was true for NTM conserved epitopes, suggesting that intragenus conservation also influences host pathogen adaptation. The biological relevance of this observation was demonstrated further by several observations. First, the T cells elicited by MTB/NTM cross-reactive epitopes in HCs were found mainly in a CCR6 + CXCR3 + memory subset, similar to findings in LTBI individuals. Thus, both MTB and NTM appear to elicit a phenotypically similar T-cell response. Second, T cells reactive to MTB/NTMconserved epitopes responded to naturally processed epitopes from MTB and NTMs, whereas T cells reactive to MTB-specific epitopes responded only to MTB. Third, cross-reactivity could be translated to antigen recognition. Several MTB candidate vaccine antigens were cross-reactive, but others were MTB-specific. Finally, NTM-specific epitopes that elicit T cells that recognize NTMs but not MTB were identified. These epitopes can be used to characterize T-cell responses to NTMs, eliminating the confounding factor of MTB cross-recognition and providing insights into vaccine design and evaluation.tuberculosis | T-cell epitope | NTM | epitope conservation | T-cell subset

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“…In spite of macrophages being the first cells to encounter the tuberculosis pathogens and their capacity to phagocyte and destroy bacteria, mycobacteria may reside/ replicate within their phagosome (Baena & Porcelli 2009, Behar et al 2010. Therefore, the main cell type correlated with resistance after TB infection is the CD4 lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Cellular immune response of Curraleiro Pé-duro and Nellore calves following Mycobacterium bovis-BCG vaccination

et al. 2013

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The present study aimed to assess the CD4, CD8 and γδ blood levels for Curraleiro Pé-duro, as well as the specific IFN-γ response after BCG vaccination using flow cytometry. The specific immune response against BCG was also evaluated by tuberculin skin test, performed before and 45 days after the vaccination. For comparison purposes, the same parameters were investigated on Nellore calves, an exotic bovine with resistance previously demonstrated. Naturally, Curraleiro Pé-duro animals had greater levels of CD4, CD8 and γδ lymphocytes (p<0.05). In response to vaccine, Curraleiro Pé-duro showed greater ability to respond specifically to BCG, generating resistance profile (Th1), evidenced by greater number of antigen specific CD4+ cells producing IFN-γ (p<0.05) and also higher tuberculin skin test reaction (p<0.05). Additionally, vaccinated Curraleiro Pé-duro calves had higher CD4 cells numbers than both Nellore control (p<0.05) and vaccinated groups (p<0.05). Curraleiro Pé-duro calves' higher basal lymphocytes blood level and stronger response in both IFN-γ and tuberculin skin test parameters probably play a positive role on protection/resistance to Mycobacterium bovis.

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Evasion and subversion of antigen presentation by Mycobacterium tuberculosis

Cited by 131 publications

References 145 publications

Dormant Mycobacterium tuberculosis Fails To Block Phagosome Maturation and Shows Unexpected Capacity To Stimulate Specific Human T Lymphocytes

Dormant Mycobacterium tuberculosis Fails To Block Phagosome Maturation and Shows Unexpected Capacity To Stimulate Specific Human T Lymphocytes

Immunological consequences of intragenus conservation ofMycobacterium tuberculosisT-cell epitopes

Cellular immune response of Curraleiro Pé-duro and Nellore calves following Mycobacterium bovis-BCG vaccination

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