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. Following a severe primary infection, the risk of developing pneumonia increases due to acquired immune defects collectively known as sepsis-induced immunosuppression. Roquilly et al. show that resolution of the primary infection changed the local environment, leading to the development of DCs and macrophages that are functionally impaired in terms of T cell activation, and instead exhibit tolerogenic properties that contribute to immune suppression.
| Original language | English |
|---|---|
| Pages (from-to) | 135-147.e5 |
| Number of pages | 17 |
| Journal | Immunity |
| Volume | 47 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 18 Jul 2017 |
Keywords
- Bacterial Infection
- Dendritic Cells
- Influenza Virus
- interleukin 12
- mucosal immunology
- Natural Killer Cells
- pneumonia
- Transforming Growth Factor Beta
- Trauma
- Treg cells
Cite this
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Local Modulation of Antigen-Presenting Cell Development after Resolution of Pneumonia Induces Long-Term Susceptibility to Secondary Infections. / Roquilly, Antoine; McWilliam, Hamish E.G.; Jacqueline, Cedric; Tian, Zehua; Cinotti, Raphael; Rimbert, Marie; Wakim, Linda; Caminschi, Irina; Lahoud, Mireille H.; Belz, Gabrielle T.; Kallies, Axel; Mintern, Justine D.; Asehnoune, Karim; Villadangos, Jose A.
In: Immunity, Vol. 47, No. 1, 18.07.2017, p. 135-147.e5.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Local Modulation of Antigen-Presenting Cell Development after Resolution of Pneumonia Induces Long-Term Susceptibility to Secondary Infections
AU - Roquilly, Antoine
AU - McWilliam, Hamish E.G.
AU - Jacqueline, Cedric
AU - Tian, Zehua
AU - Cinotti, Raphael
AU - Rimbert, Marie
AU - Wakim, Linda
AU - Caminschi, Irina
AU - Lahoud, Mireille H.
AU - Belz, Gabrielle T.
AU - Kallies, Axel
AU - Mintern, Justine D.
AU - Asehnoune, Karim
AU - Villadangos, Jose A.
PY - 2017/7/18
Y1 - 2017/7/18
N2 - 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. Following a severe primary infection, the risk of developing pneumonia increases due to acquired immune defects collectively known as sepsis-induced immunosuppression. Roquilly et al. show that resolution of the primary infection changed the local environment, leading to the development of DCs and macrophages that are functionally impaired in terms of T cell activation, and instead exhibit tolerogenic properties that contribute to immune suppression.
AB - 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. Following a severe primary infection, the risk of developing pneumonia increases due to acquired immune defects collectively known as sepsis-induced immunosuppression. Roquilly et al. show that resolution of the primary infection changed the local environment, leading to the development of DCs and macrophages that are functionally impaired in terms of T cell activation, and instead exhibit tolerogenic properties that contribute to immune suppression.
KW - Bacterial Infection
KW - Dendritic Cells
KW - Influenza Virus
KW - interleukin 12
KW - mucosal immunology
KW - Natural Killer Cells
KW - pneumonia
KW - Transforming Growth Factor Beta
KW - Trauma
KW - Treg cells
UR - http://www.scopus.com/inward/record.url?scp=85026634372&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2017.06.021
DO - 10.1016/j.immuni.2017.06.021
M3 - Article
VL - 47
SP - 135-147.e5
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 1
ER -