Expression of Proinflammatory and Regulatory Cytokines via NF-κB and MAPK-Dependent and IFN Regulatory Factor-3-Independent Mechanisms in Human Primary Monocytes Infected by Mycobacterium tuberculosis
Knowledge of the molecular events regulating the innate response to Mycobacterium tuberculosis (Mtb) is critical for understanding immunological pathogenesis and protection from tuberculosis. To this aim, the regulation and the expression of regulatory and proinflammatory cytokines were investigated...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2011/841346 |
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| author | Elena Giacomini Maria Elena Remoli Marta Scandurra Valérie Gafa Manuela Pardini Lanfranco Fattorini Eliana M. Coccia |
| author_facet | Elena Giacomini Maria Elena Remoli Marta Scandurra Valérie Gafa Manuela Pardini Lanfranco Fattorini Eliana M. Coccia |
| author_sort | Elena Giacomini |
| collection | DOAJ |
| description | Knowledge of the molecular events regulating the innate response to Mycobacterium tuberculosis (Mtb) is critical for understanding immunological pathogenesis and protection from tuberculosis. To this aim, the regulation and the expression of regulatory and proinflammatory cytokines were investigated in human primary monocytes upon Mtb infection. We found that Mtb-infected monocytes preferentially express a proinflammatory cytokine profile, including IL-6, TNF-α, and IL-1β. Conversely, among the regulatory cytokines, Mtb elicited IL-10 and IL-23 release while no expression of IL-12p70, IL-27, and IFN-β was observed. The analysis of the signalling pathways leading to this selective cytokine expression showed that in monocytes Mtb activates MAPK and NF-κB but is unable to stimulate IRF-3 phosphorylation, a transcription factor required for IL-12p35 and IFN-β gene expression. Thus, by inducing a specific cytokine profile, Mtb can influence the immunoregulatory properties of monocytes, which represent important target of novel vaccinal strategies against Mtb infection. |
| format | Article |
| id | doaj-art-46950c89e6a843acabf8d303018d6367 |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-46950c89e6a843acabf8d303018d63672025-02-03T06:01:22ZengWileyClinical and Developmental Immunology1740-25221740-25302011-01-01201110.1155/2011/841346841346Expression of Proinflammatory and Regulatory Cytokines via NF-κB and MAPK-Dependent and IFN Regulatory Factor-3-Independent Mechanisms in Human Primary Monocytes Infected by Mycobacterium tuberculosisElena Giacomini0Maria Elena Remoli1Marta Scandurra2Valérie Gafa3Manuela Pardini4Lanfranco Fattorini5Eliana M. Coccia6Dipartimento di Malattie Infettive, Parassitarie ed Immmuno-mediate, Istituto Superiore di Sanità, I-00161, Rome, ItalyDipartimento di Malattie Infettive, Parassitarie ed Immmuno-mediate, Istituto Superiore di Sanità, I-00161, Rome, ItalyDipartimento di Malattie Infettive, Parassitarie ed Immmuno-mediate, Istituto Superiore di Sanità, I-00161, Rome, ItalyDipartimento di Malattie Infettive, Parassitarie ed Immmuno-mediate, Istituto Superiore di Sanità, I-00161, Rome, ItalyDipartimento di Malattie Infettive, Parassitarie ed Immmuno-mediate, Istituto Superiore di Sanità, I-00161, Rome, ItalyDipartimento di Malattie Infettive, Parassitarie ed Immmuno-mediate, Istituto Superiore di Sanità, I-00161, Rome, ItalyDipartimento di Malattie Infettive, Parassitarie ed Immmuno-mediate, Istituto Superiore di Sanità, I-00161, Rome, ItalyKnowledge of the molecular events regulating the innate response to Mycobacterium tuberculosis (Mtb) is critical for understanding immunological pathogenesis and protection from tuberculosis. To this aim, the regulation and the expression of regulatory and proinflammatory cytokines were investigated in human primary monocytes upon Mtb infection. We found that Mtb-infected monocytes preferentially express a proinflammatory cytokine profile, including IL-6, TNF-α, and IL-1β. Conversely, among the regulatory cytokines, Mtb elicited IL-10 and IL-23 release while no expression of IL-12p70, IL-27, and IFN-β was observed. The analysis of the signalling pathways leading to this selective cytokine expression showed that in monocytes Mtb activates MAPK and NF-κB but is unable to stimulate IRF-3 phosphorylation, a transcription factor required for IL-12p35 and IFN-β gene expression. Thus, by inducing a specific cytokine profile, Mtb can influence the immunoregulatory properties of monocytes, which represent important target of novel vaccinal strategies against Mtb infection.http://dx.doi.org/10.1155/2011/841346 |
| spellingShingle | Elena Giacomini Maria Elena Remoli Marta Scandurra Valérie Gafa Manuela Pardini Lanfranco Fattorini Eliana M. Coccia Expression of Proinflammatory and Regulatory Cytokines via NF-κB and MAPK-Dependent and IFN Regulatory Factor-3-Independent Mechanisms in Human Primary Monocytes Infected by Mycobacterium tuberculosis Clinical and Developmental Immunology |
| title | Expression of Proinflammatory and Regulatory Cytokines via NF-κB and MAPK-Dependent and IFN Regulatory Factor-3-Independent Mechanisms in Human Primary Monocytes Infected by Mycobacterium tuberculosis |
| title_full | Expression of Proinflammatory and Regulatory Cytokines via NF-κB and MAPK-Dependent and IFN Regulatory Factor-3-Independent Mechanisms in Human Primary Monocytes Infected by Mycobacterium tuberculosis |
| title_fullStr | Expression of Proinflammatory and Regulatory Cytokines via NF-κB and MAPK-Dependent and IFN Regulatory Factor-3-Independent Mechanisms in Human Primary Monocytes Infected by Mycobacterium tuberculosis |
| title_full_unstemmed | Expression of Proinflammatory and Regulatory Cytokines via NF-κB and MAPK-Dependent and IFN Regulatory Factor-3-Independent Mechanisms in Human Primary Monocytes Infected by Mycobacterium tuberculosis |
| title_short | Expression of Proinflammatory and Regulatory Cytokines via NF-κB and MAPK-Dependent and IFN Regulatory Factor-3-Independent Mechanisms in Human Primary Monocytes Infected by Mycobacterium tuberculosis |
| title_sort | expression of proinflammatory and regulatory cytokines via nf κb and mapk dependent and ifn regulatory factor 3 independent mechanisms in human primary monocytes infected by mycobacterium tuberculosis |
| url | http://dx.doi.org/10.1155/2011/841346 |
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