Tumor Necrosis Factor Blockade in Chronic Murine Tuberculosis Enhances Granulomatous Inflammation and Disorganizes Granulomas in the Lungs

Chakravarty, Soumya D.; Zhu, Guofeng; Tsai, Ming Chih; Mohan, Vellore P.; Marino, Simeone; Kirschner, Denise E.; Huang, Lu-Qi; Flynn, Jo Anne L.; Chan, John

doi:10.1128/iai.01011-07

Cited by 124 publications

(100 citation statements)

References 47 publications

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“…In a subsequent study, the same group of investigators used laser capture microdissection to study gene expression of lung lesions within 1 week after TNF-␣ neutralization, when lung bacterial burdens were equivalent in the experimental and control groups, and found enhanced expression of genes encoding the proinflammatory cytokines IFN-␥ and IL-12p40, as well as those encoding the chemokines CCR6 and CCL20 in the experimental group (160). They speculated that altered chemokine expression may have led to B cell mistrafficking and the observed dissolution of B lymphocyte aggregates (160), which appear to be required for optimal control of M. tuberculosis infection (161). Additional studies have confirmed the importance of TNF-␣ in controlling paucibacillary infection and preventing reactivation.…”

Section: Tnf-␣mentioning

confidence: 89%

Latent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms

Dutta

Karakousis

2014

Microbiol Mol Biol Rev

201

174

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SUMMARY The aim of this review is to present the current state of knowledge on human latent tuberculosis infection (LTBI) based on clinical studies and observations, as well as experimental in vitro and animal models. Several key terms are defined, including “latency,” “persistence,” “dormancy,” and “antibiotic tolerance.” Dogmas prevalent in the field are critically examined based on available clinical and experimental data, including the long-held beliefs that infection is either latent or active, that LTBI represents a small population of nonreplicating, “dormant” bacilli, and that caseous granulomas are the haven for LTBI. The role of host factors, such as CD4 + and CD8 + T cells, T regulatory cells, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ), in controlling TB infection is discussed. We also highlight microbial regulatory and metabolic pathways implicated in bacillary growth restriction and antibiotic tolerance under various physiologically relevant conditions. Finally, we pose several clinically important questions, which remain unanswered and will serve to stimulate future research on LTBI.

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Section: Tnf-␣mentioning

confidence: 89%

Latent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms

Dutta

Karakousis

2014

Microbiol Mol Biol Rev

201

174

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“…Whereas IFN-g and TNF can be produced by innate immune cells, T cells are potent producers of these cytokines and have been shown to be critical for controlling mycobacterial infection in animal models and humans (Szabo et al 2003;Al-Muhsen and Casanova 2008;Kwan and Ernst 2011;Philips and Ernst 2012;Tubo and Jenkins 2014). Mice deficient in CD4 þ T cells, IFN-g signaling, or TNF signaling show disorganized macrophage aggregates that become necrotic (Kindler et al 1989;Flynn et al 1993Flynn et al , 1995Bean et al 1999;Caruso et al 1999;Scanga et al 2000;Flynn and Chan 2001;Roach et al 2002;Algood et al 2005;Stenger 2005;Chakravarty et al 2008;Wallis and Schluger 2010). These observations associated granuloma formation with a protective immune response to TB.…”

Section: Summary: a New Role For The Granuloma From A Historical Persmentioning

confidence: 99%

Immunity and Immunopathology in the Tuberculous Granuloma

Pagán

Ramakrishnan

2014

Cold Spring Harb Perspect Med

144

131

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“…Since TNF is also critical for establishing competent mycobacterial granulomas (16), perturbation of the IL-10-TNF balance should lead to disruption of the granulomatous control of M. tuberculosis infection. The influence of IL-10 on granuloma formation has not been fully elucidated; however, granuloma formation is moderately altered in IL-10 KO/anti-IL-10R-treated mycobacterial models (21,39,57,120) as well as in models with other pathogens (135).…”

Section: Il-10 Dampens Tnf-mediated Inflammation During Infectionmentioning

confidence: 99%

Interleukin-10 and Immunity against Prokaryotic and Eukaryotic Intracellular Pathogens

2011

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2The generation of an effective immune response against an infection while also limiting tissue damage requires a delicate balance between pro-and anti-inflammatory responses. Interleukin-10 (IL-10) has potent immunosuppressive effects and is essential for regulation of immune responses. However, the immunosuppressive properties of IL-10 can also be exploited by pathogens to facilitate their own survival. In this minireview, we discuss the role of IL-10 in modulating intracellular bacterial, fungal, and parasitic infections. Using information from several different infection models, we bring together and highlight some common pathways for IL-10 regulation and function that cannot be fully appreciated by studies of a single pathogen.

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Tumor Necrosis Factor Blockade in Chronic Murine Tuberculosis Enhances Granulomatous Inflammation and Disorganizes Granulomas in the Lungs

Cited by 124 publications

References 47 publications

Latent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms

Latent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms

Immunity and Immunopathology in the Tuberculous Granuloma

Interleukin-10 and Immunity against Prokaryotic and Eukaryotic Intracellular Pathogens

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