The onset of adaptive immunity in the mouse model of tuberculosis and the factors that compromise its expression

Robinson, Richard; Orme, Ian M.; Cooper, Andrea M.

doi:10.1111/imr.12259

Cited by 36 publications

(29 citation statements)

References 126 publications

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“…This manipulation occurs from the start of the human Mtb interaction when immune surveillance cells of the lung recognize danger through binding of their pattern recognition receptors to exquisitely refined Mtb pathogen associated molecular molecules. It is this initial interaction that results in production of chemokines and cytokines which then recruit and activate inflammatory cells (9). Following this initial interaction, bacteria migrate to the draining lymph node where they initiate (quite effectively) antigen-specific T cells that differentiate into cytokine-producing cells capable of expressing a variety of chemokine receptors that allow them to traffic away from the lymph node and into sites of tissue inflammation (7, 9).…”

Section: Introductionmentioning

confidence: 99%

“…It is this initial interaction that results in production of chemokines and cytokines which then recruit and activate inflammatory cells (9). Following this initial interaction, bacteria migrate to the draining lymph node where they initiate (quite effectively) antigen-specific T cells that differentiate into cytokine-producing cells capable of expressing a variety of chemokine receptors that allow them to traffic away from the lymph node and into sites of tissue inflammation (7, 9). These antigen-specific T cells must then migrate via chemokine gradients, co-locate with Mtb-infected phagocytic cells and release cytokines which activate the infected cells to kill the Mtb (7, 9).…”

Section: Introductionmentioning

confidence: 99%

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Cytokines and Chemokines inMycobacterium tuberculosisInfection

et al. 2016

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Chemokines and cytokines are critical for initiating and coordinating the organized and sequential recruitment and activation of cells into Mycobacterium tuberculosis -infected lungs. Correct mononuclear cellular recruitment and localization are essential to ensure control of bacterial growth without the development of diffuse and damaging granulocytic inflammation. An important block to our understanding of TB pathogenesis lies in dissecting the critical aspects of the cytokine/chemokine interplay in light of the conditional role these molecules play throughout infection and disease development. Much of the data highlighted in this review appears at first glance to be contradictory, but it is the balance between the cytokines and chemokines that is critical, and the “goldilocks” (not too much and not too little) phenomenon is paramount in any discussion of the role of these molecules in TB. Determination of how the key chemokines/cytokines and their receptors are balanced and how the loss of that balance can promote disease is vital to understanding TB pathogenesis and to identifying novel therapies for effective eradication of this disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytokines and Chemokines inMycobacterium tuberculosisInfection

et al. 2016

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“…Experimental mouse models of aerosol exposure to Mtb indicate that the rapidity of bacterial dissemination and early activation of T cells in the draining lymph node and spleen contribute to effective control of lung infection 9, 10, 11 . Specifically, slow dissemination of bacteria leads to delayed T cell activation and delayed recruitment of these T cells 12 .…”

Section: Introductionmentioning

confidence: 99%

Differential expression of an alternative splice variant of IL-12Rβ1 impacts early dissemination in the mouse and associates with disease outcome in both mouse and humans exposed to tuberculosis

Das

Cai

et al. 2018

Preprint

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Experimental mouse models of TB suggest that early events in the lung impact immunity. Early events in the human lung in response to TB are difficult to probe and their impact on disease outcome is unknown. We have shown in mouse that a secreted alternatively-spliced variant of IL-12Rβ1, lacking the transmembrane domain and termed ΔTM-IL-12Rβ1, promotes dendritic cell migration to the draining lymph node, augments T cell activation and limits dissemination of M. tuberculosis (Mtb). We show here that CBA/J and C3H/HeJ mice (both highly susceptible to Mtb) express higher levels of ΔTM-IL-12Rβ1 than resistant C57BL6 mice and limit early dissemination of Mtb from the lungs. Both CD11c+ cells and T cells express ΔTM-IL-12Rβ1 in humans, and mice unable to make ΔTM-IL-12Rβ1 in either CD4 or CD11c expressing cells permit early dissemination from the lung. Analysis of publically available blood transcriptomes indicates that pulmonary TB is associated with high ΔTM-IL-12Rβ1 expression and that of all IL-12 related signals, the ΔTM-IL-12Rβ1 signal best predicts active disease. ΔTM-IL-12Rβ1 expression reflects the heterogeneity of latent TB infection and has the capacity to discriminate between latent and active disease. In a new Chinese TB patient cohort, ΔTM-IL-12Rβ1 effectively differentiates TB from latent TB, healthy controls and pneumonia patients. Finally, ΔTM-IL-12Rβ1 expression drops in drug-treated individuals in the UK and China where infection pressure is low. We propose that ΔTM-IL-12Rβ1 regulates early dissemination from the lung and that it has diagnostic potential and provides mechanistic insights into human TB.

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Section: Introductionmentioning

confidence: 99%

“…Following mycobacterial infection, multiple arms of host immune system are mobilized to defense the invasion of mycobacteria [1]. Conserved mechanisms employed by host for the recognition of Mtb are essential for the containment of bacterial infection in the early stage and instruction of specific adaptive immunity [1–5]. A delicate balance between protective immunity and destructive pathology shapes the lung environment and directs granuloma development, which eventually decides the occurrence of TB [6,7].…”

Section: Introductionmentioning

confidence: 99%

IL-37 Confers Protection against Mycobacterial Infection Involving Suppressing Inflammation and Modulating T Cell Activation

et al. 2017

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Interleukin-37 (IL-37), a novel member of the IL-1 family, plays fundamental immunosuppressive roles by broadly reducing both innate inflammation and acquired immunity, but whether it is involved in the pathogenesis of tuberculosis (TB) has not been clearly elucidated. In this study, single nucleotide polymorphism (SNP) analysis demonstrated an association of the genetic variant rs3811047 of IL-37 with TB susceptibility. In line with previous report, a significant elevated IL-37 abundance in the sera and increased expression of IL-37 protein in the peripheral blood mononuclear cells (PBMC) were observed in TB patients in comparison to healthy controls. Moreover, release of IL-37 were detected in either macrophages infected with Mycobacterium tuberculosis (Mtb) or the lung of BCG-infected mice, concurrent with reduced production of proinflammatory cytokines including IL-6 and TNF-α. Furthermore, in contrast to wild-type mice, BCG-infected IL-37-Tg mice manifested with reduced mycobacterial burden and tissue damage in the lung, accompanied by higher frequency of Th1 cell and less frequencies of regulatory T cells and Th17 cells in the spleen. Taken together, our findings demonstrated that IL-37 conferred resistance to Mtb infection possibly involving suppressing detrimental inflammation and modulating T cell responses. These findings implicated that IL-37 may be employed as a new molecular target for the therapy and diagnosis of TB.

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The onset of adaptive immunity in the mouse model of tuberculosis and the factors that compromise its expression

Cited by 36 publications

References 126 publications

Cytokines and Chemokines inMycobacterium tuberculosisInfection

Cytokines and Chemokines inMycobacterium tuberculosisInfection

Differential expression of an alternative splice variant of IL-12Rβ1 impacts early dissemination in the mouse and associates with disease outcome in both mouse and humans exposed to tuberculosis

IL-37 Confers Protection against Mycobacterial Infection Involving Suppressing Inflammation and Modulating T Cell Activation

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