Dissecting host factors that regulate the early stages of tuberculosis infection

Agrawal, Neha; Bhattacharyya, Chandrika; Mukherjee, Ankur; Ullah, Ubaid; Pandit, Bhaswati; Rao, Kanury V. S.; Majumder, Partha P.

doi:10.1016/j.tube.2016.07.009

Cited by 16 publications

(19 citation statements)

References 61 publications

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“…M. tuberculosis infections show increased IL‐17A levels in patients with acute TB, 26 as well as in in vivo mouse models 27 , 28 , 29 , 30 , 31 , 32 and in vitro human PBMC cultures 33 , 34 , 35 . Secukinumab treatment in the in vitro microgranuloma study—even at 100‐fold higher concentrations compared to adalimumab—overall did not show a change of Auramine‐O and Nile red staining, and of rifampicin resistance.…”

Section: Discussionmentioning

confidence: 90%

“…Vaccination studies with Mycobacterium bovis (bacille Calmette‐Guérin) show increased IL‐17A responses, 23 , 24 , 25 however T‐cell frequencies and cytokine expression profiles did not correlate with protection against TB after bacille Calmette‐Guérin vaccination 25 . M. tuberculosis infections have been associated with increased IL‐17A levels in patients with acute TB, 26 in in vivo mouse models, 27 , 28 , 29 , 30 , 31 , 32 as well as in in vitro human peripheral blood mononuclear cell (PBMC) cultures 33 , 34 , 35 . Early granuloma formation may be dependent on IL‐17A, 28 but IL‐17A‐induced neutrophil recruitment may also increase pathological lesions and bacterial burden in chronic pulmonary infections 36 .…”

mentioning

confidence: 99%

“…25 M. tuberculosis infections have been associated with increased IL-17A levels in patients with acute TB, 26 in in vivo mouse models, [27][28][29][30][31][32] as well as in in vitro human peripheral blood mononuclear cell (PBMC) cultures. [33][34][35] Early granuloma formation may be dependent on IL-17A, 28 but IL-17A-induced neutrophil recruitment may also increase pathological lesions and bacterial burden in chronic pulmonary infections. 36 Unlike the equivocal role of IL-17A in host resistance to M. tuberculosis infections, [18][19][20][21][22] the importance of tumor necrosis factor-α (TNFα) in immunity to this intracellular pathogen is well established, as documented clinically by the association of anti-TNFα therapies with reactivation of LTBIs, in psoriasis and rheumatoid arthritis indications.…”

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confidence: 99%

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Inhibition of IL‐17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections

et al. 2017

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Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), has been shown to have significant efficacy in the treatment of moderate to severe psoriasis, psoriatic arthritis and ankylosing spondylitis. Blocking critical mediators of immunity may carry a risk of increased opportunistic infections. Here we present clinical and in vitro findings examining the effect of secukinumab on Mycobacterium tuberculosis infection. We re-assessed the effect of secukinumab on the incidence of acute tuberculosis (TB) and reactivation of latent TB infection (LTBI) in pooled safety data from five randomized, double-blind, placebo-controlled, phase 3 clinical trials in subjects with moderate to severe plaque psoriasis. No cases of TB were observed after 1 year. Importantly, in subjects with a history of pulmonary TB (but negative for interferon-γ release and receiving no anti-TB medication) or positive for latent TB (screened by interferon-γ release assay and receiving anti-TB medication), no cases of active TB were reported. Moreover, an in vitro study examined the effect of the anti-tumor necrosis factor-α (TNFα) antibody adalimumab and secukinumab on dormant M. tuberculosis H37Rv in a novel human three-dimensional microgranuloma model. Auramine-O, Nile red staining and rifampicin resistance of M. tuberculosis were measured. In vitro, anti-TNFα treatment showed increased staining for Auramine-O, decreased Nile red staining and decreased rifampicin resistance, indicative of mycobacterial reactivation. In contrast, secukinumab treatment was comparable to control indicating a lack of effect on M. tuberculosis dormancy. To date, clinical and preclinical investigations with secukinumab found no evidence of increased M. tuberculosis infections.

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confidence: 90%

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Inhibition of IL‐17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections

et al. 2017

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“…in vitro granuloma models have been developed to study M. tuberculosis [29,[68][69][70][71][72][73][74][75][76], M. leprae [77], M. bovis [78], M. massiliense [79], and Map [44]. Unique iterations of the M. tuberculosis model were used to investigate resuscitation from latency [69,76], consequences of macrophage polarization [71], and effects of cytokine suppression on granuloma development [74]. Granuloma models of other mycobacterial pathogens provide useful comparisons to M. tuberculosis with respect to bacterial survival, host response, and optimum MOI for cluster formation.…”

Section: Discussionmentioning

confidence: 99%

Modelling Bovine Granuloma Formation In Vitro upon Infection with Mycobacterium Avium Subspecies Paratuberculosis

Rice

McDaniel

Holland

et al. 2019

Veterinary Sciences

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Mycobacterium avium subspecies paratuberculosis (Map) causes chronic granulomatous disease in cattle and ruminant livestock, causing substantial economic losses. Current vaccines delay clinical signs but cannot train the immune system to fully eradicate latent Map. During latency, Map uses host defenses, cage-like macrophage clusters called granuloma, as incubators for months or years. We used an in vitro model to investigate the early coordination of macrophages into granuloma upon Map infection over ten days. We found that at multiplicities of infection (MOI; Map:macrophages) of 1:2 and below, the macrophages readily form clusters and evolve pro-inflammatory cytokines in keeping with a cell-mediated immune response. At higher MOIs, viability of host macrophages is negatively impacted. At 1:4 MOI, we quantified viable Map in our model and confirmed that intracellular Map reproduced over the first five days of infection. Host cells expressed Type 1-specific cytokines, and Map-infected macrophages displayed reduced motility compared to Map-exposed, uninfected macrophages, suggesting an important role for uninfected macrophages in the early aggregative response. Reported is the first in vitro JD granuloma model capturing Map and macrophage viability, size distribution of resulting clusters, motility of monocyte-derived macrophages, and cytokine response during clustering, allowing quantitative analysis of multiple parameters of the Map-specific granulomatous response.

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“…Because virtually all classes of antibiotics require metabolically active bacteria for their primary mode of action, the non-replicating state of MTB within the host is thought to render MTB resistant to otherwise bactericidal antibiotics. This unique nature of the disease, specificity of location, and development of closed granulomas that contain persister bacilli [128,129] increases the need for an antimicrobial treatment that provides continuous intracellular drug concentrations within the phagocyte and granuloma to be effective.…”

Section: Second-line Oral Antituberculosis Agents (Use All Possible Dmentioning

confidence: 99%

Development of a novel anti-infectivity platform for the treatment of neglected tropical and infectious diseases

Binnebose

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Dissecting host factors that regulate the early stages of tuberculosis infection

Cited by 16 publications

References 61 publications

Inhibition of IL‐17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections

Inhibition of IL‐17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections

Modelling Bovine Granuloma Formation In Vitro upon Infection with Mycobacterium Avium Subspecies Paratuberculosis

Development of a novel anti-infectivity platform for the treatment of neglected tropical and infectious diseases

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