Evidence for a unique species-specific hypersensitive epitope in Mycobacterium tuberculosis derived cord factor

McMullen, Ashley; Hwang, Shen-An; O’Shea, Kelly; Aliru, Maureen; Actor, Jeffrey K.

doi:10.1016/s1472-9792(13)70017-9

Cited by 6 publications

(4 citation statements)

References 55 publications

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“…***P < 0.001. models. 5,12,22 The pathologic response detailed in this report resembles lung pathologic findings from M. tuberculosis infected mice at 19 weeks during the chronic phase of M. tuberculosis infection. 26 One major difference between M. tuberculosiseinduced pathologic findings and the model described here is the absence of large clusters of foamy macrophages, which are readily apparent during M. tuberculosis infection.…”

Section: Discussionsupporting

confidence: 55%

“…route reaffirm histologic findings previously identified in the mouse. 11,12,22,23 Unique features were identified in the TDM-IPIV mice that had distinct patterns of hemorrhage development and hypercoagulation. The TDM-IPIV model produced a more aggressive lung pathologic response compared with the previously published acute TDM Plaque-like formations were counted manually.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 The adaptive response is dominated with high levels of IFN-g, IL-2, and IL-12, eliciting a strong T-cell helper type 1 response. 12 Thus, TDM is capable of generating an adaptive T-cell helper type 1 immunity and the antigen-specific memory that is observed in M. tuberculosis infection.…”

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confidence: 99%

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Trehalose 6,6-Dimycolate from Mycobacterium tuberculosis Induces Hypercoagulation

Donnachie¹,

Fedotova

Hwang³

2016

The American Journal of Pathology

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Tuberculosis (TB) remains a global health concern. Trehalose 6'6-dimycolate (TDM) activates innate inflammation and likely also stimulates chronic inflammation observed during disease progression. Noninfectious models using purified TDM oil/water emulsions elicit pathologic findings observed in patients with TB. We introduce a new TDM model that promotes inflammatory lung pathologic findings and vascular occlusion and hemorrhage. C57BL/6 and BALB/c mice were injected with 10 μg of i.p. TDM in light mineral oil (TDM-IP). At day 7, another injection of 10 μg of i.v. TDM in oil/water emulsion was given (TDM-IV). The i.p./i.v. TDM (TDM-IVIP) group was compared with mice injected once with i.v. or i.p. TDM. The responses to TDM-IP, TDM-IV, or TDM-IPIV were consistent between mouse strains. Mice that received TDM-IV and TDM-IPIV had inflammatory pathologic findings with increases in inflammatory and T-cell cytokines, and the TDM-IPIV group had further enhancement of IL-10 and granulocyte-macrophage colony-stimulating factor. The TDM-IPIV group had increased CD4(+) T cells in lung tissue, significantly increased coagulation, decreased clot formation time, and increased maximum clot firmness. Masson's trichrome staining revealed increased deposition of collagen in the occluded vasculature. TDM-IPIV promotes a hypercoagulopathy state, independent of inflammation. This new model argues that TDM is sufficient to generate the hypercoagulopathy observed in patients with TB.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

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Trehalose 6,6-Dimycolate from Mycobacterium tuberculosis Induces Hypercoagulation

Donnachie¹,

Fedotova

Hwang³

2016

The American Journal of Pathology

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“…(Guidry et al 2006, 2007; Welsh et al 2010; McMullen et al 2013; Donnachie et al 2016). All cytokines analyzed for controls were at or below the level of detection for the assays and were no different from naive controls.…”

Section: Resultsmentioning

confidence: 99%

Oral recombinant human or mouse lactoferrin reducesMycobacterium tuberculosisTDM induced granulomatous lung pathology

Hwang

Kruzel

Actor

2017

Biochem. Cell Biol.

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Trehalose 6'6-dimycolate (TDM) is the most abundant glycolipid on the cell wall of Mycobacterium tuberculosis (MTB). TDM is capable of inducing granulomatous pathology in mouse models that resembles those induced by MTB infection. Using the acute TDM model, this work investigates the effect of recombinant human and mouse lactoferrin to reduce granulomatous pathology. C57BL/6 mice were injected intravenously with TDM at a dose of 25 μg-mouse-1. At day 4 and 6, recombinant human or mouse lactoferrin (1 mg · (100 μL)−1 mouse−1) were delivered by gavage. At day 7 after TDM injection, mice were evaluated for lung pathology, cytokine production, and leukocyte populations. Mice given human or mouse lactoferrin had reduced production of IL-12p40 in their lungs. Mouse lactoferrin increased IL-6 and KC (CXCL1) in lung tissue. Increased numbers of macrophages were observed in TDM-injected mice given human or mouse lactoferrin. Granulomatous pathology, composed of mainly migrated leukocytes, was visually reduced in mice that received human or mouse lactoferrin. Quantitation of granulomatous pathology demonstrated a significant decrease in mice given human or mouse lactoferrin compared with TDM control mice. This report is the first to directly compare the immune modulatory effects of both heterologous recombinant human and homologous mouse lactoferrin on the development of TDM-induced granulomas.

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Trehalose Dimycolate (Cord Factor) as a Contributing Factor to Tuberculosis Pathogenesis

Actor¹

2019

Tuberculosis Host-Pathogen Interactions

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Evidence for a unique species-specific hypersensitive epitope in Mycobacterium tuberculosis derived cord factor

Cited by 6 publications

References 55 publications

Trehalose 6,6-Dimycolate from Mycobacterium tuberculosis Induces Hypercoagulation

Trehalose 6,6-Dimycolate from Mycobacterium tuberculosis Induces Hypercoagulation

Oral recombinant human or mouse lactoferrin reducesMycobacterium tuberculosisTDM induced granulomatous lung pathology

Trehalose Dimycolate (Cord Factor) as a Contributing Factor to Tuberculosis Pathogenesis

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