Acute Granulomatous Response Produced in Mice by Trehalose-6,6-Dimycolate

Bekierkunst, A.

doi:10.1128/jb.96.4.958-961.1968

Cited by 87 publications

(40 citation statements)

References 6 publications

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“…Currently, development of mucosal vaccines against a variety of viral pathogens is gaining momentum to protect against predominant mucosal infections, such as influenza, parainfluenza, respiratory syncytial virus, rotavirus, and HIV/SIV [26,29,48,49]. Consistent with a high degree of compartmentalization, the mucosal immune system is populated by functionally distinct B cells, T cells, and accessory cell subpopulations comparable to populations present in systemic lymphoid tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Killed Mycobacterium tuberculosis is an excellent candidate adjuvant used in the preparation of Freund's complete adjuvant [27], but its use in humans and in food animals is contraindicated due to a severe granulomatous inflammatory reaction induced at the injection site. This adverse effect results from toxic cell wall components of Mtb (such as mycolic acids, arabinogalactan, wax D) [28,29]. However, adjuvanticity of various purified components of Mtb have been evaluated individually with satisfactory results [30,31].…”

Section: Introductionmentioning

confidence: 99%

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Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs

Dwivedi

Manickam

Patterson

et al. 2011

Vaccine

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Porcine reproductive and respiratory syndrome (PRRS) is an economically important disease to pork producers worldwide. Commercially, both live and killed PRRSV vaccines are available to control PRRS, but they are not always successful. Based on the results of mucosal immunization studies in other viral models, a good mucosal vaccine may be an effective way to elicit protective immunity to control PRRS outbreaks. In the present study, mucosal adjuvanticity of Mycobacterium tuberculosis whole cell lysate (Mtb WCL) was evaluated in pigs administered a modified live PRRS virus vaccine (PRRS-MLV) intranasally. A Mtb WCL mediated increase in the frequency of NK cells, CD8(+)and CD4(+) T cells, and γδ T cells in pig lungs were detected. Importantly, an increased and early generation of PRRSV specific neutralizing antibodies were detected in PRRS-MLV+ Mtb WCL compared to pigs inoculated with vaccine alone. In addition, there was an increased secretion of Th1 cytokines (IFNγ and IL-12) that correlated with a reciprocal reduction in the production of immunosuppressive cytokines (IL-10 and TGFβ) as well as T-regulatory cells in pigs vaccinated with PRRS-MLV+ Mtb WCL. Further, a complete rescue in arginase levels in the lungs mediated through Mtb WCL was observed in pigs inoculated with PRRS-MLV. In conclusion, Mtb WCL may be a potent mucosal adjuvant for PRRS-MLV in order to potentiate the anti-PRRSV specific immune responses to control PRRS effectively.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs

Dwivedi

Manickam

Patterson

et al. 2011

Vaccine

View full text Add to dashboard Cite

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“…More than 35 years ago, the glycolipid trehalose-6,6′-dimycolate (TDM) was reported to be a potent granuloma-inducing factor. Intravenous injection of mice with TDM emulsions in oil was shown to transiently induce the formation of granulomas within 1 week (Bekierkunst, 1968). In addition, phosphatidyl-myo-inositol mannosides (PIMs) have also been shown to induce granuloma formation in mice (Apostolou et al, 1999;Gilleron et al, 2001;Mempel et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Adherent-invasive Escherichia coli isolated from Crohn's disease patients induce granulomas in vitro

et al. 2007

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SummaryAdherent-invasive Escherichia coli (AIEC) have been shown to be highly associated with ileal Crohn's disease (CD). AIEC survive within infected macrophages, residing within the phagolysosomal compartment where they take advantage of the low pH to replicate extensively. We investigated whether, like the tuberculous bacillus which also persists within macrophages, AIEC LF82 induces the formation of granulomas, which are a common histopathological feature of CD. For this purpose, we have taken advantage of an in vitro model of human granulomas that we recently developed, based on blood-derived mononuclear cells. We demonstrated that AIEC LF82 induces aggregation of infected macrophages, fusion of some of them to form multinucleated giant cells and subsequent recruitment of lymphocytes. Light microscopy and scanning electron microscopy analysis of the cell aggregates confirmed their granuloma features. This was further confirmed by histological analysis of granuloma sections. Noteworthy, this phenomenon can be reproduced by soluble protein extracts of AIEC LF82 coated onto beads. Although the cell aggregates not completely mimic natural CD-associated granulomas, they are very similar to early stages of epithelioid granulomas.

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“…Heat-killed Mycobacterium tuberculosis (Mtb) in an oil emulsion has been used extensively for experimental purposes as complete Freund's adjuvant [18]. Unfortunately, adverse effects mediated by major cell wall components of Mtb such as mycolic acids, peptidoglycan, and wax D preclude use of complete Freund's adjuvant in humans and food animals [19,20]. Adjuvanticity of various purified individual components of Mtb have been investigated [21,22], including water soluble whole cell lysate (WCL) of Mtb [23].…”

Section: Introductionmentioning

confidence: 99%

Cross-protective immunity to porcine reproductive and respiratory syndrome virus by intranasal delivery of a live virus vaccine with a potent adjuvant

Dwivedi

Manickam

Patterson

et al. 2011

Vaccine

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Porcine reproductive and respiratory syndrome (PRRS) is an immunosuppressive chronic respiratory viral disease of pigs that is responsible for major economic losses to the swine industry worldwide. The efficacy of parenteral administration of widely used modified live virus PRRS vaccine (PRRS-MLV) against genetically divergent PRRSV strains remains questionable. Therefore, we evaluated an alternate and proven mucosal immunization approach by intranasal delivery of PRRS-MLV (strain VR2332) with a potent adjuvant to elicit cross-protective immunity against a heterologous PRRSV (strain MN184). Mycobacterium tuberculosis whole cell lysate (Mtb WCL) was chosen as a potent mucosal adjuvant due to its Th1 biased immune response to PRRS-MLV. Unvaccinated pigs challenged with MN184 had clinical PRRS with severe lung pathology; however, vaccinated (PRRS-MLV+ Mtb WCL) pigs challenged with MN184 were apparently healthy. There was a significant increase in the body weight gain in vaccinated compared to unvaccinated PRRSV challenged pigs. Vaccinated compared to unvaccinated, virus-challenged pigs had reduced lung pathology associated with enhanced PRRSV neutralizing antibody titers and reduced viremia. Immunologically, an increased frequency of Th cells, Th/memory cells, γδ T cells, dendritic cells, and activated Th cells and a reduced frequency of T-regulatory cells were detected at both mucosal and systemic sites. Further, reduced secretion of immunosuppressive cytokines (IL-10 and TGF-β) and upregulation of the Th1 cytokine IFN-γ in blood and lungs were detected in mucosally vaccinated, PRRSV-challenged pigs. In conclusion, intranasal immunization of pigs with PRRS-MLV administered with Mtb WCL generated effective cross-protective immunity against PRRSV.

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Acute Granulomatous Response Produced in Mice by Trehalose-6,6-Dimycolate

Cited by 87 publications

References 6 publications

Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs

Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs

Adherent-invasive Escherichia coli isolated from Crohn's disease patients induce granulomas in vitro

Cross-protective immunity to porcine reproductive and respiratory syndrome virus by intranasal delivery of a live virus vaccine with a potent adjuvant

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