The Experts below are selected from a list of 210 Experts worldwide ranked by ideXlab platform
Jan Alexander - One of the best experts on this subject based on the ideXlab platform.
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Toxic effects of mineral oil saturated hydrocarbons (MOSH) and relation to accumulation in rat Liver
Food and Chemical Toxicology, 2019Co-Authors: Unni Cecilie Nygaard, Åshild Vege, Torleiv O. Rognum, Koni Grob, Christel Cartier, Jean-pierre Cravedi, Jan AlexanderAbstract:Humans are daily exposed to mineral oil saturated hydrocarbons (MOSH) from the diet. We exposed female Fischer 344 rats to a broad mixture and sub-fractions of MOSH. Chemical characterization of the MOSH mixture used and material accumulated in rat tissues were previously reported. Rats were exposed to feed containing 0-4000 mg/kg broad MOSH mixture for 30, 60, 90 and 120 days; and for 120 days to feed containing different MOSH fractions: i) mainly molecular masses < C25 (S-C25), ii) dewaxed, mainly molecular masses > C25 (L-C25) and iii) the L-C25 fraction mixed with wax largely consisting of n-alkanes > C25 (L-C25W). Treatments related effects were increased Liver and spleen weight, as well as vacuolization and Granuloma formation with lymphoid cell clusters in the Liver, but effects varied strongly between the MOSH fractions tested. We conclude that increased Liver and spleen weights were mainly related to accumulated iso-alkanes and substituted cycloalkanes, but also wax n-alkanes. Induction of Liver Granuloma appeared to be related to n-alkanes > C25 and not to the accumulated amount of MOSH. Immune responses to an injected antigen were not affected. MOSH fractions associated with increased Liver and spleen weights were similar to those accumulating in humans.
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Toxic effects of mineral oil saturated hydrocarbons (MOSH) and relation to accumulation in rat Liver.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2018Co-Authors: Unni Cecilie Nygaard, Åshild Vege, Torleiv O. Rognum, Koni Grob, Christel Cartier, Jean-pierre Cravedi, Jan AlexanderAbstract:Abstract Humans are daily exposed to mineral oil saturated hydrocarbons (MOSH) from the diet. We exposed female Fischer 344 rats to a broad mixture and sub-fractions of MOSH. Chemical characterization of the MOSH mixture used and material accumulated in rat tissues were previously reported. Rats were exposed to feed containing 0–4000 mg/kg broad MOSH mixture for 30, 60, 90 and 120 days; and for 120 days to feed containing different MOSH fractions: i) mainly molecular masses C25 (L-C25) and iii) the L-C25 fraction mixed with wax largely consisting of n-alkanes > C25 (L-C25W). Treatments related effects were increased Liver and spleen weight, as well as vacuolization and Granuloma formation with lymphoid cell clusters in the Liver, but effects varied strongly between the MOSH fractions tested. We conclude that increased Liver and spleen weights were mainly related to accumulated iso-alkanes and substituted cycloalkanes, but also wax n-alkanes. Induction of Liver Granuloma appeared to be related to n-alkanes > C25 and not to the accumulated amount of MOSH. Immune responses to an injected antigen were not affected. MOSH fractions associated with increased Liver and spleen weights were similar to those accumulating in humans.
Nikollaq Vozhilla - One of the best experts on this subject based on the ideXlab platform.
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Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation
Nature Immunology, 2017Co-Authors: Uma Mahesh Gundra, Natasha M. Girgis, Michael A. Gonzalez, Mei San Tang, Hendrik J.p. Van Der Zande, Jian-da Lin, Mireille Ouimet, Jordan Poles, Nikollaq Vozhilla, Edward A FisherAbstract:It remains unclear whether activated inflammatory macrophages can adopt features of tissue-resident macrophages, or what mechanisms might mediate such a phenotypic conversion. Here we show that vitamin A is required for the phenotypic conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80^intCD206^+PD-L2^+MHCII^+ macrophages into macrophages with a tissue-resident F4/80^hiCD206^−PD-L2^−MHCII^−UCP1^+ phenotype in the peritoneal cavity of mice and during the formation of Liver Granulomas in mice infected with Schistosoma mansoni . The phenotypic conversion of F4/80^intCD206^+ macrophages into F4/80^hiCD206^− macrophages was associated with almost complete remodeling of the chromatin landscape, as well as alteration of the transcriptional profiles. Vitamin A–deficient mice infected with S. mansoni had disrupted Liver Granuloma architecture and increased mortality, which indicates that failure to convert macrophages from the F4/80^intCD206^+ phenotype to F4/80^hiCD206^− may lead to dysregulated inflammation during helminth infection. Loke and colleagues show that vitamin A is required for the conversion of interleukin 4 (IL-4)-activated monocyte-derived macrophages into macrophages with a tissue-resident phenotype in the peritoneal cavity and in S. mansoni –induced Liver Granulomas in mice.
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Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation
Nature immunology, 2017Co-Authors: Uma Mahesh Gundra, Natasha M. Girgis, Michael A. Gonzalez, Mei San Tang, Hendrik J.p. Van Der Zande, Jian-da Lin, Mireille Ouimet, Lily J, Jordan Poles, Nikollaq VozhillaAbstract:It remains unclear whether activated inflammatory macrophages can adopt features of tissue-resident macrophages, or what mechanisms might mediate such a phenotypic conversion. Here we show that vitamin A is required for the phenotypic conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80intCD206+PD-L2+MHCII+ macrophages into macrophages with a tissue-resident F4/80hiCD206-PD-L2-MHCII-UCP1+ phenotype in the peritoneal cavity of mice and during the formation of Liver Granulomas in mice infected with Schistosoma mansoni. The phenotypic conversion of F4/80intCD206+ macrophages into F4/80hiCD206- macrophages was associated with almost complete remodeling of the chromatin landscape, as well as alteration of the transcriptional profiles. Vitamin A-deficient mice infected with S. mansoni had disrupted Liver Granuloma architecture and increased mortality, which indicates that failure to convert macrophages from the F4/80intCD206+ phenotype to F4/80hiCD206- may lead to dysregulated inflammation during helminth infection.
Dov L. Boros - One of the best experts on this subject based on the ideXlab platform.
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Retroviral Foxp3 gene transfer ameliorates Liver Granuloma pathology in Schistosoma mansoni infected mice.
Immunology, 2005Co-Authors: Kameshwar P. Singh, Hervé C. Gérard, Alan P. Hudson, Thipparthi R. Reddy, Dov L. BorosAbstract:Schistosomiasis mansoni, a tropical helminthic disease, is caused by disseminated worm eggs that induce CD4(+) T-cell mediated Granulomatous inflammation and fibrosis. T suppressor cell activity has been proposed as one of the mechanisms active in the down-modulation of the murine disease during the chronic stage (16-20 weeks of the infection). In recent years a new category of the CD4(+) CD25(+) T regulatory (Treg) lymphocyte has been identified that maintains immune tolerance to self, and also functions in the regulation of parasite-induced immunopathology. The Foxp3 gene which encodes the transcription factor Scurfin was found to be expressed by and required for the generation of CD4(+) CD25(+) T reg. At 8 weeks of the infection Foxp3 gene expression of splenocytes was similar to that of naive mice, but increased fourfold by 16 weeks. In contrast, Granulomatous Livers at 8 and 16 weeks showed 10- and 30-fold increases, respectively, in gene expression compared with normal Liver. The percentage of Granuloma CD4(+) CD25(+) T cells rose from 12% at 8 weeks to 88% at 16 weeks of the infection. Foxp3 expression was 3.5-fold higher in the CD4(+) CD25(+) versus the CD4(+) CD25(-) T cells in the 8 week infection Granulomas. As a novel observation neuropilin-1 membrane expression, a recently identified marker for Treg, was correlated with Foxp3 expression in the Granuloma CD4(+) CD25(+) but not the CD25(-) cells. Co-incubation with polyclonal stimulation of CD4(+) CD25(+) splenic cells with CD4(+) CD25(-) cells suppressed proliferation of the latter. Retroviral transfer of the Foxp3 gene at the onset of Granuloma formation enhanced fourfold Foxp3 expression in the Granuloma CD4(+) CD25(+) T cells and strongly suppressed full Granuloma development. Gene transfer also significantly enhanced transforming growth factor-beta, interferon-gamma and interleukin-4 but not interleukin-10 expression. It is concluded, that CD4(+) CD25(+), Foxp3(+) Treg cells also regulate schistosome egg-induced immunopathology.
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Enhanced Th1 and Dampened Th2 Responses Synergize To Inhibit Acute Granulomatous and Fibrotic Responses in Murine Schistosomiasis Mansoni
Infection and immunity, 1999Co-Authors: Dov L. Boros, Joel R. WhitfieldAbstract:In murine schistosomiasis mansoni, the CD4+ T-helper (Th)-cell population (12, 21, 26) initiates and maintains the Granulomatous inflammatory response around disseminated worm eggs (6). Over the past several years, Th0, Th1, and Th2 subsets of lymphocytes have been implicated in the generation of Granuloma formation (10, 32, 40). In the lung Granuloma model, as well as in infected mice, analysis of cytokine mRNA message and expression showed an early Th0-Th1 profile, which shifted to a predominant Th2 pattern with the maturation of the Granulomas (3, 11, 19, 37). Moreover, cross-regulation by Th1- and Th2-type cytokines has been demonstrated; gamma interferon (IFN-γ) and interleukin-12 (IL-12) were shown to downregulate the IL-4-mediated Granuloma response (20, 24), whereas IL-4 (9) and IL-10 regulated IFN-γ and IL-2 production (14, 15, 29, 38). Recently, a strong regulatory role has been described for IL-12 in the lung Granulomatous response of naive or sensitized mice, which was mediated by IFN-γ (36). Thus, the generation of a strong Th1 response proved to be effective in the suppression of the florid development of the Th2-type Granuloma. This impressive suppression could not be duplicated in infected mice, because repeated injections of exogenous recombinant IL-12 (rIL-12) into egg-primed and subsequently infected mice showed only moderate inhibition of Liver Granuloma development (33). Based on our previous observation that established the predominant Th1-type IFN-γ cytokine response of the early-developing Liver Granulomas (19), we intended to prolong this Th1 phase by the administration of exogenous rIL-12 and to examine its suppressive effect on the development of the Granulomas and the cytokine production profile. Here we show that when we found the proper time window for treatment, prolonged Th1 responsiveness achieved significant suppression of the hepatic Granulomatous response and decreased collagen deposition in the tissues.
Uma Mahesh Gundra - One of the best experts on this subject based on the ideXlab platform.
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Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation
Nature Immunology, 2017Co-Authors: Uma Mahesh Gundra, Natasha M. Girgis, Michael A. Gonzalez, Mei San Tang, Hendrik J.p. Van Der Zande, Jian-da Lin, Mireille Ouimet, Jordan Poles, Nikollaq Vozhilla, Edward A FisherAbstract:It remains unclear whether activated inflammatory macrophages can adopt features of tissue-resident macrophages, or what mechanisms might mediate such a phenotypic conversion. Here we show that vitamin A is required for the phenotypic conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80^intCD206^+PD-L2^+MHCII^+ macrophages into macrophages with a tissue-resident F4/80^hiCD206^−PD-L2^−MHCII^−UCP1^+ phenotype in the peritoneal cavity of mice and during the formation of Liver Granulomas in mice infected with Schistosoma mansoni . The phenotypic conversion of F4/80^intCD206^+ macrophages into F4/80^hiCD206^− macrophages was associated with almost complete remodeling of the chromatin landscape, as well as alteration of the transcriptional profiles. Vitamin A–deficient mice infected with S. mansoni had disrupted Liver Granuloma architecture and increased mortality, which indicates that failure to convert macrophages from the F4/80^intCD206^+ phenotype to F4/80^hiCD206^− may lead to dysregulated inflammation during helminth infection. Loke and colleagues show that vitamin A is required for the conversion of interleukin 4 (IL-4)-activated monocyte-derived macrophages into macrophages with a tissue-resident phenotype in the peritoneal cavity and in S. mansoni –induced Liver Granulomas in mice.
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Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation
Nature immunology, 2017Co-Authors: Uma Mahesh Gundra, Natasha M. Girgis, Michael A. Gonzalez, Mei San Tang, Hendrik J.p. Van Der Zande, Jian-da Lin, Mireille Ouimet, Lily J, Jordan Poles, Nikollaq VozhillaAbstract:It remains unclear whether activated inflammatory macrophages can adopt features of tissue-resident macrophages, or what mechanisms might mediate such a phenotypic conversion. Here we show that vitamin A is required for the phenotypic conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80intCD206+PD-L2+MHCII+ macrophages into macrophages with a tissue-resident F4/80hiCD206-PD-L2-MHCII-UCP1+ phenotype in the peritoneal cavity of mice and during the formation of Liver Granulomas in mice infected with Schistosoma mansoni. The phenotypic conversion of F4/80intCD206+ macrophages into F4/80hiCD206- macrophages was associated with almost complete remodeling of the chromatin landscape, as well as alteration of the transcriptional profiles. Vitamin A-deficient mice infected with S. mansoni had disrupted Liver Granuloma architecture and increased mortality, which indicates that failure to convert macrophages from the F4/80intCD206+ phenotype to F4/80hiCD206- may lead to dysregulated inflammation during helminth infection.
John H Brumell - One of the best experts on this subject based on the ideXlab platform.
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listeriolysin o allows listeria monocytogenes replication in macrophage vacuoles
Nature, 2008Co-Authors: Cheryl L Birmingham, Veronica Canadien, Natalia A Kaniuk, Benjamin Steinberg, Darren E Higgins, John H BrumellAbstract:Listeria monocytogenes is an intracellular bacterial pathogen that replicates rapidly in the cytosol of host cells during acute infection. Surprisingly, these bacteria were found to occupy vacuoles in Liver Granuloma macrophages during persistent infection of severe combined immunodeficient (SCID) mice. Here we show that L. monocytogenes can replicate in vacuoles within macrophages. In Livers of SCID mice infected for 21 days, we observed bacteria in large LAMP1(+) compartments that we termed spacious Listeria-containing phagosomes (SLAPs). SLAPs were also observed in vitro, and were found to be non-acidic and non-degradative compartments that are generated in an autophagy-dependent manner. The replication rate of bacteria in SLAPs was found to be reduced compared to the rate of those in the cytosol. Listeriolysin O (LLO, encoded by hly), a pore-forming toxin essential for L. monocytogenes virulence, was necessary and sufficient for SLAP formation. A L. monocytogenes mutant with low LLO expression was impaired for phagosome escape but replicated slowly in SLAPs over a 72 h period. Therefore, our studies reveal a role for LLO in promoting L. monocytogenes replication in vacuoles and suggest a mechanism by which this pathogen can establish persistent infection in host macrophages.
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Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles
Nature, 2008Co-Authors: Cheryl L Birmingham, Veronica Canadien, Natalia A Kaniuk, Darren E Higgins, Benjamin E. Steinberg, John H BrumellAbstract:The bacterial pathogen Listeria monocytogenes is a common a cause of infection in immunocompromised individuals and in pregnancy. It multiplies rapidly in the cytosol of infected cells, but was recently found in intracellular vacuoles in a mouse model of the disease. A closer study of these vacuoles in mice during persistent listeriosis reveals them as sites of comparably slow bacterial replication which may promote bacterial survival in the face of the host immune response. Listeria monocytogenes is an intracellular bacterial pathogen that replicates rapidly in the cytosol of host cells during acute infection^ 1 . Surprisingly, these bacteria were found to occupy vacuoles in Liver Granuloma macrophages during persistent infection of severe combined immunodeficient (SCID) mice^ 2 . Here we show that L. monocytogenes can replicate in vacuoles within macrophages. In Livers of SCID mice infected for 21 days, we observed bacteria in large LAMP1^+ compartments that we termed spacious Listeria -containing phagosomes (SLAPs). SLAPs were also observed in vitro , and were found to be non-acidic and non-degradative compartments that are generated in an autophagy-dependent manner. The replication rate of bacteria in SLAPs was found to be reduced compared to the rate of those in the cytosol. Listeriolysin O (LLO, encoded by hly ), a pore-forming toxin essential for L. monocytogenes virulence^ 1 , was necessary and sufficient for SLAP formation. A L. monocytogenes mutant with low LLO expression was impaired for phagosome escape but replicated slowly in SLAPs over a 72 h period. Therefore, our studies reveal a role for LLO in promoting L. monocytogenes replication in vacuoles and suggest a mechanism by which this pathogen can establish persistent infection in host macrophages. Listeria monocytogenes multiplies rapidly in the cytosol of infected cells, but has also been found in intracellular vacuoles during persistent infection. Now, these vacuoles are described as sites of comparably slow bacterial replication, which may promote bacterial survival in face of the host immune response.