Role of Interleukin (IL)‐1 Type 1 Receptor in Mycobacterial Infection

Sugawara, Isamu; Yamada, Hiroyuki; Hua, Shuncheng; Mizuno, Satoru

doi:10.1111/j.1348-0421.2001.tb01310.x

Cited by 84 publications

(78 citation statements)

References 23 publications

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“…Neutrophil depletion during early mycobacterial infection exacerbates disease and dysregulates granuloma formation (23)(24)(25)(26). However neutrophils are associated with tissue damage and necrosis in late disease and are a feature of granulomas in gene-deletion models associated with increased susceptibility to tuberculosis (27)(28)(29)(30)(31)(32)(33). Neutrophils release mediators that likely contributed to the angiogenesis in the trehalose mycolate-bearing matrices, evident at 4 days postinjection (34).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Activity of Released Cell Wall Lipids ofMycobacterium bovisBacillus Calmette-Guérin Is Due Principally to Trehalose Mycolates

Geisel

Sakamoto

Russell

et al. 2005

The Journal of Immunology

171

154

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The hallmark of Mycobacterium-induced pathology is granulomatous inflammation at the site of infection. Mycobacterial lipids are potent immunomodulators that contribute to the granulomatous response and are released in appreciable quantities by intracellular bacilli. Previously we investigated the granulomagenic nature of the peripheral cell wall lipids of Mycobacterium bovis bacillus Calmette-Guérin (BCG) by coating the lipids onto 90-μm diameter microspheres that were mixed into Matrigel matrix with syngeneic bone marrow-derived macrophages and injected i.p. into mice. These studies demonstrated that BCG lipids elicit proinflammatory cytokines and recruit leukocytes. In the current study we determined the lipids responsible for this proinflammatory effect. BCG-derived cell wall lipids were fractionated and purified by liquid chromatography and preparative TLC. The isolated fractions including phosphatidylinositol dimannosides, cardiolipin, phosphatidylglycerol, phosphatidylethanolamine, trehalose monomycolate, trehalose dimycolate, and mycoside B. Trehalose dimycolate, when delivered to bone marrow-derived murine macrophages, induced the greatest secretion of IL-1β, IL-6, and TNF-α in vitro. Trehalose dimycolate similarly induced the greatest secretion of these proinflammatory cytokines in ex vivo matrices over the course of 12 days. Trehalose monomycolate and dimycolate also induced profound neutrophil recruitment in vivo. Experiments with TLR2 or TLR4 gene-deficient mice revealed no defects in responses to trehalose mycolates, although MyD88-deficient mice manifested significantly reduced cell recruitment and cytokine production. These results demonstrate that the trehalose mycolates, particularly trehalose dimycolate, are the most bioactive lipids in the BCG extract, inducing a proinflammatory cascade that influences granuloma formation.

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Section: Discussionmentioning

confidence: 99%

In Vivo Activity of Released Cell Wall Lipids ofMycobacterium bovisBacillus Calmette-Guérin Is Due Principally to Trehalose Mycolates

Geisel

Sakamoto

Russell

et al. 2005

The Journal of Immunology

171

154

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“…all showing greater susceptibility to tuberculosis (25,26). In addition, IL-18 has also been shown to play a role in protective immunity to tuberculosis (27).…”

Section: Original Researchmentioning

confidence: 99%

Type 2 Diabetes Mellitus Coincident with Pulmonary Tuberculosis Is Associated with Heightened Systemic Type 1, Type 17, and Other Proinflammatory Cytokines

et al. 2013

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Rationale: Type 2 diabetes mellitus is a major risk factor for the development of active tuberculosis, although the biological basis underlying this susceptibility remains poorly characterized. Objectives and Methods:To identify the influence of coincident diabetes mellitus on cytokine levels in pulmonary tuberculosis, we examined circulating levels of a panel of cytokines and chemokines in the plasma of individuals with tuberculosis with diabetes and compared them with those of individuals without diabetes. Measurements and Main Results:Tuberculosis with diabetes is characterized by elevated circulating levels of type 1 (IFN-g, tumor necrosis factor-a, and IL-2), type 2 (IL-5), and type 17 (IL-17A) cytokines but decreased circulating levels of IL-22. This was associated with increased systemic levels of other proinflammatory cytokines (IL-1b, IL-6, and IL-18) and an antiinflammatory cytokine (IL-10) but not type 1 IFNs. Moreover, tuberculosis antigenstimulated whole blood also showed increased levels of proinflammatory cytokines. Finally, type 1 and type 17 cytokines in plasma exhibit a significant positive correlation with hemoglobin A1C levels, indicating that impaired control of diabetes is associated with this proinflammatory milieu. Multivariate analysis revealed that the association of proinflammatory cytokines with diabetes mellitus was not influenced by age, sex, or other metabolic parameters.Conclusions: Our data reveal that tuberculosis with diabetes is characterized by heightened cytokine responsiveness, indicating that chronic inflammation underlying type 2 diabetes potentially contributes to increased immune pathology and poor control in tuberculosis infection.

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“…The lungs from STAT1 KO mice treated subcutaneously with recombinant IL-12 were retrieved from the infected mice 5 weeks after aerosol infection . The sizes of the 10 granulomas were measured with a micrometer (Nikon Optical Co., Tokyo) (Sugawara et al 2001a).…”

Section: Reconstitution Of Stat1 Ko Mice With Exogenous Recombinant Imentioning

confidence: 99%

“…We have been interested in the roles of transcription factors that regulate cytokine expression in mycobacterial infection. Nuclear factor (NF)-IL-6 is critical in mycobacterial control as well as in the induction of granulocyte-colony-stimulating factor (G-CSF) in alveolar macrophages that results in neutrophil activation (Sugawara et al 2001a). NF-B p50 KO mice developed multifocal necrotic pulmonary lesions or lobar pneumonia .…”

mentioning

confidence: 99%