Mycobacterium tuberculosis Strains Are Differentially Recognized by TLRs with an Impact on the Immune Response

Carmona, Jenny Andrea; Cruz, Andrea; Moreira-Teixeira, Lúcia; Sousa, Carole; Sousa, Jeremy; Osório, Nuno S.; Saraiva, Ana Laura; Svenson, Stefan B.; Källenius, Gunilla; Pedrosa, Jorge; Rodrigues, Fernando; Castro, António G.; Saraiva, Margarida

doi:10.1371/journal.pone.0067277

Cited by 79 publications

(94 citation statements)

References 56 publications

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“…For example, compared with the M. tuberculosis H37Rv strain, M. tuberculosis strains from the East Asian lineage induce a distinct immunopathological response in mouse models, with larger areas of pneumonia and relatively less granulomatous lung tissue 79,80 . These differences in immunopathology have been linked, at least partially, to differences in the production of distinct cell wall glycolipids 81 , which result in the differential activation of Toll-like receptors and resulting inflammatory responses 82–85 .…”

Section: Bacterial Heterogeneitymentioning

confidence: 99%

Heterogeneity in tuberculosis

2017

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Infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), results in a range of clinical presentations in humans. Most infections manifest as a clinically asymptomatic, contained state that is termed latent TB infection (LTBI); a smaller subset of infected individuals present with symptomatic, active TB. Within these two seemingly binary states, there is a spectrum of host outcomes that have varying symptoms, microbiologies, immune responses and pathologies. Recently, it has become apparent that there is diversity of infection even within a single individual. A good understanding of the heterogeneity that is intrinsic to TB — at both the population level and the individual level — is crucial to inform the development of intervention strategies that account for and target the unique, complex and independent nature of the local host–pathogen interactions that occur in this infection. In this Review, we draw on model systems and human data to discuss multiple facets of TB biology and their relationship to the overall heterogeneity observed in the human disease.

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Section: Bacterial Heterogeneitymentioning

confidence: 99%

Heterogeneity in tuberculosis

2017

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“…Yet, Wang et al [162] did not find any differences between Beijing strains. Some of the variable cytokine profiles elicited by the distinct groups of strains within Lineage 2 have been linked to differential toll-like receptor recognition [164]. Only one study has investigated intra-lineage variation within Lineage 4 but found no difference between the so-called H and T families of strains [160].…”

Section: The Consequences Of Genomic Diversity In Mtbcmentioning

confidence: 99%

Consequences of genomic diversity in Mycobacterium tuberculosis

Coscollá

Gagneux

2014

Seminars in Immunology

389

370

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The causative agent of human tuberculosis, Mycobacterium tuberculosis complex (MTBC), comprises seven phylogenetically distinct lineages associated with different geographical regions. Here we review the latest findings on the nature and amount of genomic diversity within and between MTBC lineages. We then review recent evidence for the effect of this genomic diversity on mycobacterial phenotypes measured experimentally and in clinical settings. We conclude that overall, the most geographically widespread Lineage 2 (includes Beijing) and Lineage 4 (also known as Euro-American) are more virulent than other lineages that are more geographically restricted. This increased virulence is associated with delayed or reduced pro-inflammatory host immune responses, greater severity of disease, and enhanced transmission. Future work should focus on the interaction between MTBC and human genetic diversity, as well as on the environmental factors that modulate these interactions.

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Section: Introductionmentioning

confidence: 99%

“…We recently showed that, although most of the M. tuberculosis strains tested primarily activate TLR2, some activate TLR4 (15). TLR4 activation by M. tuberculosis was found to result in the expression of host-protective factors (e.g., TNF, IFN-γ, and NOS2) and to limit bacterial growth during in vivo infection (15). Despite the protective role of TLR4, a hypervirulent strain of M. tuberculosis recognized predominantly by this receptor was also found to induce high levels of type I IFN during infection (15), a cytokine that was associated with exacerbated disease (16, 17).…”

Section: Introductionmentioning

confidence: 99%

“…TLR4 activation by M. tuberculosis was found to result in the expression of host-protective factors (e.g., TNF, IFN-γ, and NOS2) and to limit bacterial growth during in vivo infection (15). Despite the protective role of TLR4, a hypervirulent strain of M. tuberculosis recognized predominantly by this receptor was also found to induce high levels of type I IFN during infection (15), a cytokine that was associated with exacerbated disease (16, 17). Infection with other hypervirulent strains of M. tuberculosis showed a correlation between increased levels of type I IFN and increased virulence in mouse models of M. tuberculosis infection (18–20).…”

Section: Introductionmentioning

confidence: 99%

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Type I IFN Inhibits Alternative Macrophage Activation during Mycobacterium tuberculosis Infection and Leads to Enhanced Protection in the Absence of IFN-γ Signaling

Moreira-Teixeira

Sousa

McNab

et al. 2016

The Journal of Immunology

Self Cite

100

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Tuberculosis causes ∼1.5 million deaths every year, thus remaining a leading cause of death from infectious diseases in the world. A growing body of evidence demonstrates that type I IFN plays a detrimental role in tuberculosis pathogenesis, likely by interfering with IFN-γ–dependent immunity. In this article, we reveal a novel mechanism by which type I IFN may confer protection against Mycobacterium tuberculosis infection in the absence of IFN-γ signaling. We show that production of type I IFN by M. tuberculosis–infected macrophages induced NO synthase 2 and inhibited arginase 1 gene expression. In vivo, absence of both type I and type II IFN receptors led to strikingly increased levels of arginase 1 gene expression and protein activity in infected lungs, characteristic of alternatively activated macrophages. This correlated with increased lung bacterial burden and pathology and decreased survival compared with mice deficient in either receptor. Increased expression of other genes associated with alternatively activated macrophages, as well as increased expression of Th2-associated cytokines and decreased TNF expression, were also observed. Thus, in the absence of IFN-γ signaling, type I IFN suppressed the switching of macrophages from a more protective classically activated phenotype to a more permissive alternatively activated phenotype. Together, our data support a model in which suppression of alternative macrophage activation by type I IFN during M. tuberculosis infection, in the absence of IFN-γ signaling, contributes to host protection.

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Mycobacterium tuberculosis Strains Are Differentially Recognized by TLRs with an Impact on the Immune Response

Cited by 79 publications

References 56 publications

Heterogeneity in tuberculosis

Heterogeneity in tuberculosis

Consequences of genomic diversity in Mycobacterium tuberculosis

Type I IFN Inhibits Alternative Macrophage Activation during Mycobacterium tuberculosis Infection and Leads to Enhanced Protection in the Absence of IFN-γ Signaling

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