Article ; Online: Local Modulation of Antigen-Presenting Cell Development after Resolution of Pneumonia Induces Long-Term Susceptibility to Secondary Infections.
2017 Volume 47, Issue 1, Page(s) 135–147.e5
Abstract: Lung infections cause prolonged immune alterations and elevated susceptibility to secondary ... immunosuppression, reveal prognostic markers of susceptibility to secondary infections and identify potential ... pneumonia. We found that, after resolution of primary viral or bacterial pneumonia, dendritic cells (DC ...
| Abstract | Lung infections cause prolonged immune alterations and elevated susceptibility to secondary pneumonia. We found that, after resolution of primary viral or bacterial pneumonia, dendritic cells (DC), and macrophages exhibited poor antigen-presentation capacity and secretion of immunogenic cytokines. Development of these "paralyzed" DCs and macrophages depended on the immunosuppressive microenvironment established upon resolution of primary infection, which involved regulatory T (Treg) cells and the cytokine TGF-β. Paralyzed DCs secreted TGF-β and induced local Treg cell accumulation. They also expressed lower amounts of IRF4, a transcription factor associated with increased antigen-presentation capacity, and higher amounts of Blimp1, a transcription factor associated with tolerogenic functions, than DCs present during primary infection. Blimp1 expression in DC of humans suffering sepsis or trauma correlated with severity and complicated outcomes. Our findings describe mechanisms underlying sepsis- and trauma-induced immunosuppression, reveal prognostic markers of susceptibility to secondary infections and identify potential targets for therapeutic intervention. |
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| MeSH term(s) | Aged ; Animals ; Antigen Presentation ; Cell Differentiation ; Cells, Cultured ; Dendritic Cells/immunology ; Escherichia coli ; Escherichia coli Infections/immunology ; Female ; Humans ; Immune Tolerance ; Influenza A virus/immunology ; Interferon Regulatory Factors/genetics ; Interferon Regulatory Factors/metabolism ; Macrophages/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Orthomyxoviridae Infections/immunology ; Pneumonia/immunology ; Positive Regulatory Domain I-Binding Factor 1 ; Sepsis/immunology ; T-Lymphocytes, Regulatory/immunology ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transforming Growth Factor beta/genetics ; Transforming Growth Factor beta/metabolism | ||||||||||
| Chemical Substances | Interferon Regulatory Factors ; Prdm1 protein, mouse ; Transcription Factors ; Transforming Growth Factor beta ; interferon regulatory factor-4 ; Positive Regulatory Domain I-Binding Factor 1 (EC 2.1.1.-) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2017-07-18 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article | ||||||||||
| ZDB-ID | 1217235-2 | ||||||||||
| ISSN | 1097-4180 ; 1074-7613 | ||||||||||
| ISSN (online) | 1097-4180 | ||||||||||
| ISSN | 1074-7613 | ||||||||||
| DOI | 10.1016/j.immuni.2017.06.021 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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