Gene Expression Signatures in Tuberculosis Have Greater Overlap with Autoimmune Diseases Than with Infectious Diseases

Clayton, Kalum; Polak, Marta E.; Woelk, Christopher H.; Elkington, Paul

doi:10.1164/rccm.201706-1248le

Cited by 18 publications

(14 citation statements)

References 10 publications

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“…Experimental investigation into a potential autoimmune process in pulmonary TB is challenging, as the antigen is unknown and indeed autoimmunity may not be driven by a single antigen. Further support for an overlap of fundamental processes in TB and autoimmune disease came from analysis of gene expression signatures in circulating immune cells (Figure 5) [97]. Comparison of infectious disease, autoimmune disease and TB showed that there was a greater overlap between autoimmune disease and TB than between TB and other infections.…”

Section: Adverse Effects Of Excessive Inflammation In Tbmentioning

confidence: 94%

Pathogenesis of ocular tuberculosis: New observations and future directions

2020

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Ocular tuberculosis (OTB) encompasses all forms of intra-and extra-ocular inflammation associated with Mycobacterium tuberculosis (Mtb) infection. However, the organism is rarely found in ocular fluid samples of diseased eyes, rendering the pathomechanisms of the disease unclear. This confounds clinical decision-making in diagnosis and treatment of OTB.Here, we critically review existing human and animal data related to ocular inflammation and TB pathogenesis to unravel likely pathomechanisms of OTB. Broadly there appear to be two fundamental mechanisms that may underlie the development of TB-associated ocular inflammation: a. inflammatory response to live/ replicating Mtb in the eye, and b. immune mediated ocular inflammation induced by non-viable Mtb or its components in the eye. This distinction is significant as in direct Mtb-driven mechanisms, diagnosis and treatment would be aimed at detection of Mtb-infection and its elimination; while indirect mechanisms would primarily require anti-inflammatory therapy with adjunctive anti-TB therapy. Further, we discuss how that most clinical phenotypes of OTB likely represent a combination of both mechanisms, with one being predominant than the other.

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Section: Adverse Effects Of Excessive Inflammation In Tbmentioning

confidence: 94%

Pathogenesis of ocular tuberculosis: New observations and future directions

2020

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“…Previously, we have developed systems immunology pipelines which allowed us to identify the molecular basis of the orchestration of immunity by DC, revealing potential molecular targets for immune interventions. 13 , 14 Similar approaches have led to identification of molecular signatures capable of predicting the efficacy of vaccine-induced immunity and examining the transcriptional and cellular responses in P. falciparum CHMI models. 15 , 16 …”

Section: Introductionmentioning

confidence: 99%

Malaria systems immunology: Plasmodium vivax induces tolerance during primary infection through dysregulation of neutrophils and dendritic cells

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Arévalo‐Herrera

et al. 2018

Journal of Infection

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“…However, an alternative yet controversial theory, based on the small numbers of bacteria observed and several observations related to autoimmunity seen in patients with TB, proposes a role for autoimmunity: mycobacteria induce inappropriate host responses to self-antigens, causing autoimmune inflammation ( Elkington et al, 2016 ). A considerable overlap in gene expression signatures between TB and autoimmune diseases, greater than seen with other infectious diseases, supports this theory ( Clayton et al, 2017 ).…”

Section: Cavities Bronchiectasis and Fibrosismentioning

confidence: 95%

The Immune Mechanisms of Lung Parenchymal Damage in Tuberculosis and the Role of Host-Directed Therapy

et al. 2018

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Impaired lung function is common in people with a history of tuberculosis. Host-directed therapy added to tuberculosis treatment may reduce lung damage and result in improved lung function. An understanding of the pathogenesis of pulmonary damage in TB is fundamental to successfully predicting which interventions could be beneficial. In this review, we describe the different features of TB immunopathology that lead to impaired lung function, namely cavities, bronchiectasis, and fibrosis. We discuss the immunological processes that cause lung damage, focusing on studies performed in humans, and using chest radiograph abnormalities as a marker for pulmonary damage. We highlight the roles of matrix metalloproteinases, neutrophils, eicosanoids and cytokines, like tumor necrosis factor-α and interleukin 1β, as well as the role of HIV co-infection. Finally, we focus on various existing drugs that affect one or more of the immunological mediators of lung damage and could therefore play a role as host-directed therapy.

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Gene Expression Signatures in Tuberculosis Have Greater Overlap with Autoimmune Diseases Than with Infectious Diseases

Cited by 18 publications

References 10 publications

Pathogenesis of ocular tuberculosis: New observations and future directions

Pathogenesis of ocular tuberculosis: New observations and future directions

Malaria systems immunology: Plasmodium vivax induces tolerance during primary infection through dysregulation of neutrophils and dendritic cells

The Immune Mechanisms of Lung Parenchymal Damage in Tuberculosis and the Role of Host-Directed Therapy

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