Mycobacterium bovis BCG promotes IL-10 expression by establishing a SYK/PKCα/β positive autoregulatory loop that sustains STAT3 activation

Mycobacterium ensures its survival inside macrophages and long-term infection by subverting the innate and adaptive immune response through the modulation of cytokine gene expression profiles. Different Mycobacterium species promote the expression of TGFβ and IL-10, which, at the early stages of inf...

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Bibliographic Details
Published inPathogens and disease Vol. 77; no. 3
Main Authors Villaseñor, Tomás, Madrid-Paulino, Edgardo, Maldonado-Bravo, Rafael, Pérez-Martínez, Leonor, Pedraza-Alva, Gustavo
Format Journal Article
LanguageEnglish
Published United States Oxford University Press 01.04.2019
Subjects
Adaptive immunity
Bacillus Calmette-Guerin vaccine
BCG
Cell activation
Cytokines
Feedback loops
Gene Expression
Gene Expression Regulation
Gene Regulatory Networks
Humans
Immune response
Immunomodulation
Infections
Interleukin 10
Interleukin-10 - biosynthesis
Macrophages
Monocytes - immunology
Mycobacterium
Mycobacterium bovis
Mycobacterium bovis - immunology
Phagocytosis
Positive feedback
Protein kinase C
Protein Kinase C beta - metabolism
Protein Kinase C-alpha - metabolism
Signal transduction
Stat3 protein
STAT3 Transcription Factor - metabolism
Survival
Syk Kinase - metabolism
Syk protein
THP-1 Cells
Transduction
γ-Interferon
M. bovis BCG
PKC
SYK
IL-10 gene expression
STAT3
Macrophage
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Summary:Mycobacterium ensures its survival inside macrophages and long-term infection by subverting the innate and adaptive immune response through the modulation of cytokine gene expression profiles. Different Mycobacterium species promote the expression of TGFβ and IL-10, which, at the early stages of infection, block the formation of the phagolysosome, thereby securing mycobacterial survival upon phagocytosis, and at later stages, antagonize IFNγ production and functions. Despite the key role of IL-10 in mycobacterium infection, the signal transduction pathways leading to IL-10 expression in infected macrophages are poorly understood. Here, we report that Mycobacterium bovis BCG promotes IL-10 expression and cytokine production by establishing a SYK/PKCα/β positive feedback loop that leads to STAT3 activation.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:2049-632X
2049-632X
DOI:10.1093/femspd/ftz032