Involvement of Stat1 in the Phagocytosis of M. avium

Mycobacterium avium is an intracellular pathogen preferentially infecting human macrophages where they activate the JAK/STAT1 pathway. This activation enhances the survival of infected cells, but, at the same time, makes macrophages optimal targets for drugs development against p-tyr701stat1. In thi...

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Main Authors: Sabrina Dominici, Giuditta Fiorella Schiavano, Mauro Magnani, Costantina Buondelmonte, Angela Gabriela Celeste, Giorgio Brandi
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2012/652683
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author Sabrina Dominici
Giuditta Fiorella Schiavano
Mauro Magnani
Costantina Buondelmonte
Angela Gabriela Celeste
Giorgio Brandi
author_facet Sabrina Dominici
Giuditta Fiorella Schiavano
Mauro Magnani
Costantina Buondelmonte
Angela Gabriela Celeste
Giorgio Brandi
author_sort Sabrina Dominici
collection DOAJ
description Mycobacterium avium is an intracellular pathogen preferentially infecting human macrophages where they activate the JAK/STAT1 pathway. This activation enhances the survival of infected cells, but, at the same time, makes macrophages optimal targets for drugs development against p-tyr701stat1. In this study, we demonstrate that the fast and transient activity of the JAK/STAT1 pathway occurs immediately after macrophages internalization of heat-killed M. avium or inert particles. Furthermore, we show that a persistent Stat1 pathway activation occurs only when an intracellular M. avium infection is established in macrophages. These results strongly indicate different mechanisms of p-tyr701Stat1 activation. In particular, here we report findings aiming at explaining the short-time enhancement of p-tyr701Stat1 and shows its predominant relationship with FcγRs engagement during the internalization process. Furthermore, we demonstrate that opsonized live M. avium is phagocytosed by macrophages involving membrane receptors not related with JAK/STAT1 signalling pathway. On the contrary, heat-inactivated bacilli or latex particles seem to be internalized only after involvement of FcγRs and subsequent Stat1 phosphorylation.
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series Clinical and Developmental Immunology
spelling doaj-art-734ae0d3d976490fbcc1660bfbae02e52025-02-03T01:23:58ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/652683652683Involvement of Stat1 in the Phagocytosis of M. aviumSabrina Dominici0Giuditta Fiorella Schiavano1Mauro Magnani2Costantina Buondelmonte3Angela Gabriela Celeste4Giorgio Brandi5Section of Biochemistry and Molecular Biology, Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Via Saffi No. 2, 61029 Urbino, ItalySection of Toxicological Hygienic and Environmental Sciences, Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Via Saffi No. 2, 61029 Urbino, ItalySection of Biochemistry and Molecular Biology, Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Via Saffi No. 2, 61029 Urbino, ItalySection of Biochemistry and Molecular Biology, Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Via Saffi No. 2, 61029 Urbino, ItalySection of Toxicological Hygienic and Environmental Sciences, Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Via Saffi No. 2, 61029 Urbino, ItalySection of Toxicological Hygienic and Environmental Sciences, Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Via Saffi No. 2, 61029 Urbino, ItalyMycobacterium avium is an intracellular pathogen preferentially infecting human macrophages where they activate the JAK/STAT1 pathway. This activation enhances the survival of infected cells, but, at the same time, makes macrophages optimal targets for drugs development against p-tyr701stat1. In this study, we demonstrate that the fast and transient activity of the JAK/STAT1 pathway occurs immediately after macrophages internalization of heat-killed M. avium or inert particles. Furthermore, we show that a persistent Stat1 pathway activation occurs only when an intracellular M. avium infection is established in macrophages. These results strongly indicate different mechanisms of p-tyr701Stat1 activation. In particular, here we report findings aiming at explaining the short-time enhancement of p-tyr701Stat1 and shows its predominant relationship with FcγRs engagement during the internalization process. Furthermore, we demonstrate that opsonized live M. avium is phagocytosed by macrophages involving membrane receptors not related with JAK/STAT1 signalling pathway. On the contrary, heat-inactivated bacilli or latex particles seem to be internalized only after involvement of FcγRs and subsequent Stat1 phosphorylation.http://dx.doi.org/10.1155/2012/652683
spellingShingle Sabrina Dominici
Giuditta Fiorella Schiavano
Mauro Magnani
Costantina Buondelmonte
Angela Gabriela Celeste
Giorgio Brandi
Involvement of Stat1 in the Phagocytosis of M. avium
Clinical and Developmental Immunology
title Involvement of Stat1 in the Phagocytosis of M. avium
title_full Involvement of Stat1 in the Phagocytosis of M. avium
title_fullStr Involvement of Stat1 in the Phagocytosis of M. avium
title_full_unstemmed Involvement of Stat1 in the Phagocytosis of M. avium
title_short Involvement of Stat1 in the Phagocytosis of M. avium
title_sort involvement of stat1 in the phagocytosis of m avium
url http://dx.doi.org/10.1155/2012/652683
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AT costantinabuondelmonte involvementofstat1inthephagocytosisofmavium
AT angelagabrielaceleste involvementofstat1inthephagocytosisofmavium
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