TNF in Host Resistance to Tuberculosis Infection

Quesniaux, Valérie; Jacobs, Muazzam; Allie, Nasiema; Grivennikov, Sergei I.; Nedospasov, Sergei A.; García, Irene; Olleros, Maria-Luisa; Shebzukhov, Yuriy V.; Kuprash, Dmitry V.; Vasseur, Virginie; Rose, Stéphanie; Court, Nathalie; Vacher, Rachel; Ryffel, Bernhard

doi:10.1159/000289204

Cited by 56 publications

(48 citation statements)

References 139 publications

(186 reference statements)

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“…Thus, induction and activation of NFATc1 by TNF provide a mechanistic explanation by which TNF can induce giant cell formation in infectious granulomas such as in Mycobacterium tuberculosis infection (38) and in TNF-driven chronic granulomatous diseases such as sarcoidosis (39). In addition to fusion and osteoclastogenesis, NFAT regulates cytokine production, including TNF production, in myeloid cells (14,15,35) and thus can play an important role in myeloid cell biology independently of osteoclast differentiation.…”

Section: Tnf Primes Macrophages For Increased and More Rapid Responsementioning

confidence: 99%

TNF activates calcium–nuclear factor of activated T cells (NFAT)c1 signaling pathways in human macrophages

Yarilina

Chen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

116

122

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Acute activation of cells by tumor necrosis factor (TNF) has been well characterized, but little is known about later phases of TNF responses that are relevant for cells exposed to TNF for several days during inflammation. We found that prolonged exposure of human macrophages to TNF resulted in a wave of delayed but sustained activation of c-Jun and nuclear factor κB (NF-κB) proteins and of calcium oscillations that became apparent 1-3 d after TNF stimulation. These signaling events culminated in the induction and activation of the calcium-dependent transcription factor, nuclear factor of activated T cells (NFAT)c1, which mediated a gene expression program leading to cell fusion and osteoclast differentiation. TNF-induced NFATc1 activity primed macrophages for enhanced osteoclastogenesis in response to RANKL. High NFATc1 expression was apparent in synovial macrophages in a subset of patients with TNF-driven inflammatory arthritis. Thus, long-term exposure to TNF activates calcium-dependent signaling and an NFATc1-mediated gene activation program important for cell fusion and osteoclastogenesis. These findings identify a signaling pathway activated by TNF that is important for myeloid cell differentiation and suggest a role for TNF-induced calcium and NFAT signaling in chronic inflammation and associated bone resorption.calcium signaling | polykaryon

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Section: Tnf Primes Macrophages For Increased and More Rapid Responsementioning

confidence: 99%

TNF activates calcium–nuclear factor of activated T cells (NFAT)c1 signaling pathways in human macrophages

Yarilina

Chen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

116

122

View full text Add to dashboard Cite

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“…The proinflammatory cytokines like IL-12 and TNF-␣, secreted by the macrophages, are considered to be critical for conferring protection against infection with Mycobacterium tuberculosis (3)(4)(5). However, anti-inflammatory cytokines like IL-10 produced by the activated macrophages favor a T-helper 2 (Th2) 4 type of immune response by inhibiting production of protective cytokines, promoting bacterial survival, and associating with chronic progression of tuberculosis (6 -10).…”

mentioning

confidence: 99%

Endocytosis of Mycobacterium tuberculosis Heat Shock Protein 60 Is Required to Induce Interleukin-10 Production in Macrophages*

Parveen

Varman

Nair

et al. 2013

Journal of Biological Chemistry

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Background: Mtbhsp60 induces TLR2-mediated anti-inflammatory response in macrophages, but the mechanisms are not well understood. Results: Clathrin-dependent TLR2-mediated endocytosis of Mtbhsp60 is required to induce anti-inflammatory response via p38 MAPK activation. Conclusion: Mtbhsp60 induces anti-inflammatory response upon endocytosis. Blockage of endocytosis predominantly leads to pro-inflammatory cytokine production. Significance: This information is important to tailor the Mtbhsp60-triggered IL-10 signaling to specifically block the excess nonprotective Th2-type response.

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“…In comparison with conventional vaccines, DNA vaccines induce substantial cellular immunity which mainly depends on antigen-specific Th1 responses and is associated with IFN-γ and TNF-α production (20). However, studies on the efficiency of DNA vaccines expressing a single MTB antigen in the protection against TB are limited (21).…”

Section: Discussionmentioning

confidence: 99%

T-bet acts as a powerful adjuvant in Ag85B DNA‑based vaccination against tuberculosis

Zhang

et al. 2012

Mol Med Report

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Abstract. Owing to the limitations of traditional BacillusCalmette-Guerin vaccines and the low efficacy of DNA vaccines expressing single antigens of Mycobacterium tuberculosis, there is a pressing requirement for adjuvants capable of strengthing the immunogenicity and effectiveness of these vaccines against tuberculosis (TB). T-bet (TBX21) is a transcription factor, which controls the optimal development of type-1 immune responses responsible for the potent protection of vaccines against TB. However, little is known about the efficiency of the TB vaccine combined with T-bet. In this study, we report an approach to intensify the immunogenicity of Ag85B DNA-based vaccines using T-bet as an adjuvant. Balb/c mice were immunized by 3 intramuscular inoculations with pcDNA3.1-FLAG-T-bet in combination with pcDNA3.1-FLAG-Ag85B, and the immune responses were compared with those induced by vaccination with Ag85B DNA alone. We found that pcDNA3.1-T-bet-Ag85B not only induced evidently higher IgG2a antibody responses, but also increased the production of interferon-γ (IFN-γ) and interleukin (IL)-2 with the concomitant repression of IL-4 and IL-10 compared with pcDNA3.1-Ag85B alone or the empty vector. Thus, plasmid DNA coding for T-bet enhanced Ag85B-specific immune responses and shifted them to a predominant Th1-type immune response. In conclusion, T-bet is an efficacious Th1-inducing adjuvant in the context of the Ag85B DNA-based vaccination, and could also prove to be a promising candidate for DNA vaccine development against TB.

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TNF in Host Resistance to Tuberculosis Infection

Cited by 56 publications

References 139 publications

TNF activates calcium–nuclear factor of activated T cells (NFAT)c1 signaling pathways in human macrophages

TNF activates calcium–nuclear factor of activated T cells (NFAT)c1 signaling pathways in human macrophages

Endocytosis of Mycobacterium tuberculosis Heat Shock Protein 60 Is Required to Induce Interleukin-10 Production in Macrophages*

T-bet acts as a powerful adjuvant in Ag85B DNA‑based vaccination against tuberculosis

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