Mycobacterium Tuberculosis Heat Shock Proteins Use Diverse Toll-like Receptor Pathways to Activate Pro-inflammatory Signals

Bulut, Yasemin; Michelsen, Kathrin S.; Hayrapetian, Linda; Naiki, Yoshikazu; Spallek, Ralf; Singh, Mahavir; Arditi, Moshe

doi:10.1074/jbc.m411379200

Cited by 201 publications

(148 citation statements)

References 56 publications

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“…Possibly, as Hsp70 is an evolutionary conserved antigen with high homology with other bacterial and even eukaryotic Hsp70, cross-reactive T-cell responses obscured vaccine-specific T-cell responses. In addition, it has also been shown that mycobacterial Hsp70 specifically binds to innate receptors present on macrophages [29] and dendritic cells [30], leading to production of pro-inflammatory signals, which may in turn lead to IFN-␥ production by T and NK cells. The observation that all animals in this study have high frequencies of monocytes, gradually decreasing with age, adds to this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterial 70kD heat-shock protein is an effective subunit vaccine against bovine paratuberculosis

Koets

Hoek

Langelaar

et al. 2006

Vaccine

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Paratuberculosis is a chronic granulomatous inflammation of the small intestine of cattle and other ruminants, caused by infection with Mycobacterium avium ssp. paratuberculosis (MAP). The disease can be found in ruminant herds worldwide, causing substantial economic losses at farm level due to premature culling and production losses.In previous studies, it has been shown that immune responses to recombinant MAP Hsp70 proteins were predominantly cell mediated. As protective immunity to the intracellular mycobacterial pathogens is thought to be cell-mediated in origin, we have studied the use of a recombinant MAP Hsp70 as a subunit vaccine in cattle experimentally infected with MAP.The results of the current study demonstrate that recombinant MAP Hsp70 can be successfully used as a subunit vaccine against bovine paratuberculosis, significantly reducing shedding of bacteria in feces during the first 2 years following experimental infection.

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Section: Discussionmentioning

confidence: 99%

Mycobacterial 70kD heat-shock protein is an effective subunit vaccine against bovine paratuberculosis

Koets

Hoek

Langelaar

et al. 2006

Vaccine

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“…Mycobacterial HSP65 and HSP70 were shown to signal through Toll-like receptor (TLR)4 and TLR2, respectively [16]. Immunization with HSP70-peptide complexes purified from leukemia cells increased the frequency of IFN-c-secreting NK cells in the blood of the patients with chronic myelogenic leukemia [17].…”

Section: Introductionmentioning

confidence: 99%

Heat shock fusion protein induces both specific and nonspecific anti‐tumor immunity

Zhang

et al. 2006

Eur J Immunol

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Mucin 1 (MUC1) is a tumor antigen, and the most important epitopes that can induce cytotoxic T lymphocytes (CTL) reside in the variable-number tandem repeats (VNTR). Heat shock protein (HSP) complexes isolated from tumors have been shown to induce specific anti-tumor immunity. HSP alone can also induce nonspecific immunity. To explore the possibility to utilize the specific anti-tumor immunity induced by MUC1 VNTR and the nonspecific immunity induced by HSP, we constructed a recombinant protein (HSP65-MUC1) by fusing Bacillus Calmette-GuØrin-derived HSP65 with the MUC1 VNTR peptide and tested its ability to induce anti-tumor activities in a tumor challenge model. The growth of MUC1-expressing tumors was significantly inhibited in mice immunized with HSP65-MUC1, both before and after tumor challenge. A much larger percentage of immunized mice survived the tumor challenge than nonimmunized mice. Correlating with the anti-tumor activity, HSP65-MUC1 was shown to induce MUC1-specific CTL as well as nonspecific anti-tumor immunity. In the human system, HSP65-MUC1-loaded human DC induced the generation of autologous MUC1-specific CTL in vitro. These results suggest that exogenously applied HSP65-MUC1 may be used to treat MUC1 tumors by inducing the epitope-specific CTL as well as nonspecific anti-tumor responses mediated by the HSP part of the fusion protein.

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“…The role of TLR4 in M.tb infection is unclear as only a few M.tb ligands for TLR4 have been described. Recently, recombinant M.tb heat shock protein (hsp) 65 was shown to induce the generation of TLR4-dependent NFB via MyD88-, TIRAP-, TRIF-(TIR-domain-containing adapter-inducing interferon-) and TRAM-(TRIFrelated adaptor molecule)-dependent signaling pathways (Bulut et al, 2005).…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Broadening Our View About the Role of Mycobacterium tuberculosis Cell Envelope Components During Infection: A Battle for Survival

Torrelles¹

2012

Understanding Tuberculosis - Analyzing the Origin of Mycobacterium Tuberculosis Pathogenicity

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Mycobacterium Tuberculosis Heat Shock Proteins Use Diverse Toll-like Receptor Pathways to Activate Pro-inflammatory Signals

Cited by 201 publications

References 56 publications

Mycobacterial 70kD heat-shock protein is an effective subunit vaccine against bovine paratuberculosis

Mycobacterial 70kD heat-shock protein is an effective subunit vaccine against bovine paratuberculosis

Heat shock fusion protein induces both specific and nonspecific anti‐tumor immunity

Broadening Our View About the Role of Mycobacterium tuberculosis Cell Envelope Components During Infection: A Battle for Survival

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