Tuberculosis Comorbidity with Communicable and Noncommunicable Diseases

Bates, Matthew; Marais, Ben J.; Zumla, Alimuddin

doi:10.1101/cshperspect.a017889

Cited by 81 publications

(85 citation statements)

References 83 publications

(87 reference statements)

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“…Finally, while we observed an association between malnutrition and cytokine diminution, we cannot infer any causality. While we have excluded most of the known comorbidities that are known to influence cytokine responses in TB, including HIV, diabetes, and intestinal parasites (36), it is theoretically possible that other factors not examined in this study could have contributed to the differential responses. We also observed a bimodal distribution of the levels of certain cytokines that did not relate to age or gender and could be the effect of other confounders.…”

Section: Discussionmentioning

confidence: 99%

Coexistent Malnutrition Is Associated with Perturbations in Systemic and Antigen-Specific Cytokine Responses in Latent Tuberculosis Infection

Ray¹,

Munisankar²,

Bhootra³

et al. 2016

Clin Vaccine Immunol

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Section: Discussionmentioning

confidence: 99%

Coexistent Malnutrition Is Associated with Perturbations in Systemic and Antigen-Specific Cytokine Responses in Latent Tuberculosis Infection

Ray¹,

Munisankar²,

Bhootra³

et al. 2016

Clin Vaccine Immunol

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“…T cells are necessary to control Mtb infection, as mice or NHP without CD4+ or CD8+ T cells progress rapidly to active TB . HIV or SIV co‐infection, which depletes CD4+ T cells, greatly increases risk of active TB in patients and macaques …”

Section: Experimental Support For a Balanced Response In Tbmentioning

confidence: 99%

“…28,[31][32][33][34][35] HIV or SIV co-infection, which depletes CD4+ T cells, greatly increases risk of active TB in patients and macaques. 13,36,37 Anti-inflammatory responses are important for preventing excessive lung pathology during Mtb infection. [38][39][40][41][42][43] Macrophages influence inflammation in TB 44 and can be divided into subsets based on activation status (M1 or classically activated macrophages-CAM-and M2 or alternatively activated macrophages-AAM).…”

Section: E Xperimental Supp Ort For a Bal An Ced Re S P On S E In Tbmentioning

confidence: 99%

Dynamic balance of pro‐ and anti‐inflammatory signals controls disease and limits pathology

Cicchese

Evans

Hult

et al. 2018

Immunological Reviews

232

171

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Immune responses to pathogens are complex and not well understood in many diseases, and this is especially true for infections by persistent pathogens. One mechanism that allows for long-term control of infection while also preventing an over-zealous inflammatory response from causing extensive tissue damage is for the immune system to balance pro- and anti-inflammatory cells and signals. This balance is dynamic and the immune system responds to cues from both host and pathogen, maintaining a steady state across multiple scales through continuous feedback. Identifying the signals, cells, cytokines, and other immune response factors that mediate this balance over time has been difficult using traditional research strategies. Computational modeling studies based on data from traditional systems can identify how this balance contributes to immunity. Here we provide evidence from both experimental and mathematical/computational studies to support the concept of a dynamic balance operating during persistent and other infection scenarios. We focus mainly on tuberculosis, currently the leading cause of death due to infectious disease in the world, and also provide evidence for other infections. A better understanding of the dynamically balanced immune response can help shape treatment strategies that utilize both drugs and host-directed therapies.

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“…Recent modelling studies2 show that the current decline in TB incidence needs to be accelerated significantly, which cannot be achieved without developing and implementing novel tools. The increase in multidrug-resistance incidence3, the association with HIV-infection and non-communicable diseases4, the lack of an efficient vaccine and the difficulty in timely diagnosing TB5 represent just a few of the challenges that need to be addressed. Improved diagnostics6, safer and more accessible treatments for active and latent Mycobacterium tuberculosis (Mtb ) infection7 and new effective pre- and post-exposure vaccines must all be developed before we can reach TB elimination89.…”

mentioning

confidence: 99%

New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles

Coppola

Meijgaarden

Franken

et al. 2016

Sci Rep

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New strategies are needed to develop better tools to control TB, including identification of novel antigens for vaccination. Such Mtb antigens must be expressed during Mtb infection in the major target organ, the lung, and must be capable of eliciting human immune responses. Using genome-wide transcriptomics of Mtb infected lungs we developed data sets and methods to identify IVE-TB (in-vivo expressed Mtb) antigens expressed in the lung. Quantitative expression analysis of 2,068 Mtb genes from the predicted first operons identified the most upregulated IVE-TB genes during in-vivo pulmonary infection. By further analysing high-level conservation among whole-genome sequenced Mtb-complex strains (n = 219) and algorithms predicting HLA-class-Ia and II presented epitopes, we selected the most promising IVE-TB candidate antigens. Several of these were recognized by T-cells from in-vitro Mtb-PPD and ESAT6/CFP10-positive donors by proliferation and multi-cytokine production. This was validated in an independent cohort of latently Mtb-infected individuals. Significant T-cell responses were observed in the absence of IFN-γ-production. Collectively, the results underscore the power of our novel antigen discovery approach in identifying Mtb antigens, including those that induce unconventional T-cell responses, which may provide important novel tools for TB vaccination and biomarker profiling. Our generic approach is applicable to other infectious diseases.

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Tuberculosis Comorbidity with Communicable and Noncommunicable Diseases

Cited by 81 publications

References 83 publications

Coexistent Malnutrition Is Associated with Perturbations in Systemic and Antigen-Specific Cytokine Responses in Latent Tuberculosis Infection

Coexistent Malnutrition Is Associated with Perturbations in Systemic and Antigen-Specific Cytokine Responses in Latent Tuberculosis Infection

Dynamic balance of pro‐ and anti‐inflammatory signals controls disease and limits pathology

New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles

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