Tumor necrosis factor is critical to control tuberculosis infection

Jacobs, Muazzam; Togbé, Dieudonnée; Frémond, Cécile; Samarina, Arina; Allie, Nasiema; Botha, Tania; Carlos, Daniela; Parida, Shreemanta K.; Grivennikov, Sergei I.; Nedospasov, Sergei A.; Monteiro, Analbery; Bert, Marc Le; Quesniaux, Valérie; Ryffel, Bernhard

doi:10.1016/j.micinf.2007.02.002

Cited by 85 publications

(55 citation statements)

References 33 publications

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“…Indeed, even infected immune-competent human beings or animals have hardly ever been observed to eliminate the mycobacteria, resulting in a high incidence of latent infection and the reactivation of disease when the immune system is weakened. 20,21 Together, the emerging evidence supports the contemporary view that the granuloma represents a symbiotic tissue microenvironment for the mutual benefit of both the host and the mycobacterium. However, whether the mycobacterial granuloma is indeed an immunologically suppressed microenvironment remains largely to be established, and the underlying mechanisms are still unclear.…”

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confidence: 63%

Pulmonary Mycobacterial Granuloma

Shaler

Kugathasan

McCormick

et al. 2011

The American Journal of Pathology

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The granuloma, a hallmark of host defense against pulmonary mycobacterial infection, has long been believed to be an active type 1 immune environment. However, the mechanisms regarding why granuloma fails to eliminate mycobacteria even in immune-competent hosts, have remained largely unclear. By using a model of pulmonary Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection, we have addressed this issue by comparing the immune responses within the airway luminal and granuloma compartments. We found that despite having a similar immune cellular profile to that in the airway lumen, the granuloma displayed severely suppressed type 1 immune cytokine but enhanced chemokine responses. Both antigen-presenting cells (APCs) and T cells in granuloma produced fewer type 1 immune molecules including tumor necrosis factor-␣ (TNF-␣), interferon-␥ (IFN-␥), and nitric oxide. As a result, the granuloma APCs developed a reduced capacity to phagocytose mycobacteria and to induce T-cell proliferation. To examine the molecular mechanisms, we compared the levels of immune suppressive cytokine IL-10 in the airway lumen and granuloma and found that both granuloma APCs and T cells produced much more IL-10. Thus, IL-10 deficiency restored type 1 immune activation within the granuloma while having a minimal effect within the airway lumen. Hence, our study provides the first experimental evidence that, contrary to the conventional belief, the BCG-induced lung granuloma represents a symbiotic host-microbe microenvironment characterized by suppressed type 1 immune activation.

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confidence: 63%

Pulmonary Mycobacterial Granuloma

Shaler

Kugathasan

McCormick

et al. 2011

The American Journal of Pathology

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“…CD4 ϩ T cells are believed to contribute to protection against M. tuberculosis by the production of Th1 cytokines. Among these cytokines, IFN-␥ (3, 4, 22, 36) and TNF-␣ (11, 28) seem to be the central effector molecules, leading to autophagy, mycobacterial killing, and macrophage death (12,17,21,29,33). IL-2 is a potent inducer of T-cell proliferation and differentiation and is key to the optimal survival and function of memory cells (20).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Safety and Immunogenicity of Two Antigen Concentrations of the Mtb72F/AS02_ACandidate Tuberculosis Vaccine in Purified Protein Derivative-Negative Adults

Leroux-Roels

Leroux‐Roels

Ofori-Anyinam

et al. 2010

Clin Vaccine Immunol

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Tuberculosis (TB) is a major cause of illness and death worldwide, causing approximately 1.7 million deaths a year (43). Despite global efforts to control or eradicate the disease, the WHO estimates that in 2008 an estimated 8.9 million to 9.9 million people became infected with Mycobacterium tuberculosis. The situation is compounded by the emergence of multidrug-resistant TB. Since one-third of the world's population is estimated to be latently infected with M. tuberculosis and at possible risk of disease, TB prevention remains one of today's greatest public health challenges. An efficacious vaccination strategy is an essential tool to control TB.M. bovis bacillus Calmette-Guérin (BCG), consisting of attenuated strains of M. bovis, is the only TB vaccine currently available. It effectively prevents meningeal and miliary TB in young children (8) but appears to be ineffective in preventing adult-onset TB (protection rates, 0 to 80%) (10) and pulmonary TB in children.

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“…The role of TNF in protective immunity against mycobacterial infection has been extensively investigated using mice deficient for TNF signaling (9,10,13,14) or by neutralization studies (11,12). The more recent generation of mouse strains expressing only the membrane form of TNF has allowed for the investigation of the respective roles of soluble and membrane-bound TNF in host immune function during mycobacterial challenge (15)(16)(17)(18)(19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%