The Immune Response to<i>Mycobacterium tuberculosis</i>in HIV-1-Coinfected Persons

Esmail, Hanif; Riou, Catherine; Bruyn, Elsa Du; Lai, Rachel; Harley, Yolande X.R.; Meintjes, Graeme; Wilkinson, Katalin A.; Wilkinson, Robert J.

doi:10.1146/annurev-immunol-042617-053420

Cited by 107 publications

(118 citation statements)

References 232 publications

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“…While the lack of galactose is associated with inflammation in general, more specifically, agalactosylated IgG has been hypothesized to activate the mannose binding lectin complement pathway (69). This would be consistent with blood transcriptional profiling demonstrating elevated complement levels in individuals with active TB (138). The presence of sialic acid is associated with an anti-inflammatory state in rheumatological diseases (135), and this would be consistent with less inflammation in the context of latent compared to active TB (26).…”

Section: Glycosylation Patterns In Mycobacterium Tuberculosismentioning

confidence: 59%

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

McLean

Kent

et al. 2019

Front. Immunol.

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Mycobacterium tuberculosis (Mtb) resides in a quarter of the world's population and is the causative agent for tuberculosis (TB), the most common infectious reason of death in humans today. Although cellular immunity has been firmly established in the control of Mtb, there is growing evidence that antibodies may also modulate the infection. More specifically, certain antibody features are associated with inflammation and are divergent in different states of human infection and disease. Importantly, TB impacts not just the healthy but also those with chronic conditions. While HIV represents the quintessential comorbid condition for TB, recent epidemiological evidence shows that additional chronic conditions such as diabetes and kidney disease are rising. In fact, the prevalence of diabetes as a comorbid TB condition is now higher than that of HIV. These chronic diseases are themselves independently associated with proinflammatory immune states that encompass antibody profiles. This review discusses isotypes, subclasses, post-translational modifications and Fc-mediated functions of antibodies in TB infection and in the comorbid chronic conditions of HIV, diabetes, and kidney diseases. We propose that inflammatory antibody profiles, which are a marker of active TB, may be an important biomarker for detection of TB disease progression within comorbid individuals. We highlight the need for future studies to determine which inflammatory antibody profiles are the consequences of comorbidities and which may potentially contribute to TB reactivation.

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Section: Glycosylation Patterns In Mycobacterium Tuberculosismentioning

confidence: 59%

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

McLean

Kent

et al. 2019

Front. Immunol.

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“…It is well established that a pre-existing HIV infection increases susceptibility to M.tb , reflected by a higher risk of progressing to active TB following M.tb infection [3] as well as a higher risk of reactivating a latent TB infection [4]. However, the exact mechanisms by which HIV impairs host resistance to a subsequent M.tb infection are unknown [5, 6]. It is not merely due to a loss of CD4+ T cells as this effect is evident before peripheral CD4+ counts drop [7].…”

Section: Introductionmentioning

confidence: 99%

Pre-existing SIV Infection Increases Susceptibility to Tuberculosis in Mauritian Cynomolgus Macaques

Rodgers

Ameel

Ellis-Connell

et al. 2018

Preprint

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is the leading cause of death among HIV positive patients. The precise mechanisms by which HIV impairs host resistance to a subsequent M.tb infection are unknown. We modeled this co-infection in Mauritian cynomolgus macaques (MCM) using SIV as an HIV surrogate. We infected seven MCM with SIVmac239 intrarectally and six months later co-infected them via bronchoscope with ~10 CFU M.tb. Another eight MCM were infected with M.tb alone. TB progression was monitored by clinical parameters, by culturing bacilli in gastric and bronchoalveolar lavages, and by serial 18F-FDG PET/CT imaging. The eight MCM infected with M.tb alone displayed dichotomous susceptibility to TB, with four animals reaching humane endpoint within 13 weeks and four animals surviving >19 weeks post M.tb infection. In stark contrast, all seven SIV+ animals exhibited rapidly progressive TB following co-infection and all reached humane endpoint by 13 weeks. Serial PET/CT imaging confirmed dichotomous outcomes in MCM infected with M.tb alone and marked susceptibility to TB in all SIV+ MCM. Notably, imaging revealed a significant increase in TB granulomas between four and eight weeks post M.tb infection in SIV+, but not in SIV-naive MCM and implies that SIV impairs the ability of animals to contain M.tb dissemination. At necropsy, animals with pre-existing SIV infection had more extrapulmonary TB disease, more overall pathology, and increased bacterial loads than animals infected with M.tb alone. We thus developed a tractable MCM model in which to study SIV-M.tb co-infection and demonstrate that pre-existing SIV dramatically diminishes the ability to control M.tb co-infection.Author summaryMycobacterium tuberculosis (M.tb) is the etiologic agent of tuberculosis (TB) and infects a tremendous number of individuals. TB causes millions of deaths each year and is the leading cause of death in human immunodeficiency virus (HIV)-positive individuals. Currently, the mechanisms by which pre-existing HIV infection increases susceptibility to subsequent M.tb infection and predisposes an individual to TB disease are poorly understood. We developed a simian immunodeficiency virus (SIV) - M.tb co-infection model in Mauritian cynomolgus macaques (MCM) to investigate how SIV impairs the immune response to a subsequent M.tb infection. We show that naive MCM display variable resistance to TB while all SIV-infected MCM failed to control M.tb infection. Using quantitative measures of disease and serial PET/CT imaging, we show that SIV+ co-infected animals uniformly exhibit rapid TB progression, more tuberculosis disease dissemination, and increased mortality. This coinfection model will facilitate studies, provide unique insights into the defects underlying TB susceptibility in HIV+ individuals and will help us develop approaches to overcome these defects.

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“…A strong IFN-γ response is also related to high levels of other immune effector molecules, such as nuclear factor kappa-light-chainenhancer of B cells and tumour necrosis factor alpha (TNF-α), which are associated with early clearance of M. tuberculosis infection, and therefore, protection against disease [58]. Similarly, there is extensive evidence that an effective response of lymphocytes, particularly CD4+ T lymphocytes, is critical for protection against M. bovis and M. tuberculosis infection as well as TB disease progression [59][60][61][62]. For instance, the number of CD4+ T lymphocytes was the best predictor of M. tuberculosis infection risk among HIV-infected people receiving anti-retroviral therapy [62].…”

Section: Discussionmentioning

confidence: 99%

Immune stability predicts tuberculosis infection risk in a wild mammal

et al. 2019

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Immunity is one of the most variable phenotypic traits in animals; however, some individuals may show less fluctuation in immune traits, resulting in stable patterns of immune variation over time. It is currently unknown whether immune variation has consequences for infectious disease risk. In this study, we identified moderately stable immune traits in wild African buffalo and asked whether the stability of these traits affected bovine tuberculosis (TB) infection risk. We found that adaptive immune traits such as the level of interferon-γ (IFN-γ) released after white blood cell stimulation, the number of circulating lymphocytes and the level of antibodies against bovine adenovirus-3 were moderately repeatable (i.e. stable) over time, whereas parameters related to innate immunity either had low repeatability (circulating eosinophil numbers) or were not repeatable (e.g. neutrophil numbers, plasma bacteria killing capacity). Intriguingly, individuals with more repeatable IFN-γ and lymphocyte levels were at a significantly higher risk of acquiring TB infection. In stark contrast, average IFN-γ and lymphocyte levels were poor predictors of TB risk, indicating that immune variability rather than absolute response level better captured variation in disease susceptibility. This work highlights the important and under-appreciated role of immune variability as a predictor of infection risk.

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The Immune Response toMycobacterium tuberculosisin HIV-1-Coinfected Persons

Cited by 107 publications

References 232 publications

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

Pre-existing SIV Infection Increases Susceptibility to Tuberculosis in Mauritian Cynomolgus Macaques

Immune stability predicts tuberculosis infection risk in a wild mammal

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