TY - JOUR
T1 - Plasmacytoid Dendritic Cells Facilitate Th Cell Cytokine Responses throughout Schistosoma mansoni Infection
AU - Webb, Lauren M.
AU - Phythian-Adams, Alexander T.
AU - Costain, Alice H.
AU - Brown, Sheila L.
AU - Lundie, Rachel J.
AU - Forde-Thomas, Josephine
AU - Cook, Peter C.
AU - Jackson-Jones, Lucy H.
AU - Marley, Angela K.
AU - Smits, Hermelijn H.
AU - Hoffmann, Karl F.
AU - Tait Wojno, Elia D.
AU - MacDonald, Andrew S.
N1 - Copyright © 2021 The Authors.
PY - 2021/8/31
Y1 - 2021/8/31
N2 - Plasmacytoid dendritic cells (pDCs) are potent producers of type I IFN (IFN-I) during viral infection and respond to IFN-I in a positive feedback loop that promotes their function. IFN-I shapes dendritic cell responses during helminth infection, impacting their ability to support Th2 responses. However, the role of pDCs in type 2 inflammation is unclear. Previous studies have shown that pDCs are dispensable for hepatic or splenic Th2 responses during the early stages of murine infection with the trematode
Schistosoma mansoni at the onset of parasite egg laying. However, during
S. mansoni infection, an ongoing Th2 response against mature parasite eggs is required to protect the liver and intestine from acute damage and how pDCs participate in immune responses to eggs and adult worms in various tissues beyond acute infection remains unclear. We now show that pDCs are required for optimal Th2 cytokine production in response to
S. mansoni eggs in the intestinal-draining mesenteric lymph nodes throughout infection and for egg-specific IFN-γ at later time points of infection. Further, pDC depletion at chronic stages of infection led to increased hepatic and splenic pathology as well as abrogated Th2 cell cytokine production and activation in the liver. In vitro, mesenteric lymph node pDCs supported Th2 cell responses from infection-experienced CD4
+ T cells, a process dependent on pDC IFN-I responsiveness, yet independent of Ag. Together, these data highlight a previously unappreciated role for pDCs and IFN-I in maintaining and reinforcing type 2 immunity in the lymph nodes and inflamed tissue during helminth infection.
AB - Plasmacytoid dendritic cells (pDCs) are potent producers of type I IFN (IFN-I) during viral infection and respond to IFN-I in a positive feedback loop that promotes their function. IFN-I shapes dendritic cell responses during helminth infection, impacting their ability to support Th2 responses. However, the role of pDCs in type 2 inflammation is unclear. Previous studies have shown that pDCs are dispensable for hepatic or splenic Th2 responses during the early stages of murine infection with the trematode
Schistosoma mansoni at the onset of parasite egg laying. However, during
S. mansoni infection, an ongoing Th2 response against mature parasite eggs is required to protect the liver and intestine from acute damage and how pDCs participate in immune responses to eggs and adult worms in various tissues beyond acute infection remains unclear. We now show that pDCs are required for optimal Th2 cytokine production in response to
S. mansoni eggs in the intestinal-draining mesenteric lymph nodes throughout infection and for egg-specific IFN-γ at later time points of infection. Further, pDC depletion at chronic stages of infection led to increased hepatic and splenic pathology as well as abrogated Th2 cell cytokine production and activation in the liver. In vitro, mesenteric lymph node pDCs supported Th2 cell responses from infection-experienced CD4
+ T cells, a process dependent on pDC IFN-I responsiveness, yet independent of Ag. Together, these data highlight a previously unappreciated role for pDCs and IFN-I in maintaining and reinforcing type 2 immunity in the lymph nodes and inflamed tissue during helminth infection.
KW - Animals
KW - CD4-Positive T-Lymphocytes/immunology
KW - Cytokines/immunology
KW - Dendritic Cells/immunology
KW - Female
KW - Flow Cytometry/methods
KW - Host-Parasite Interactions/immunology
KW - Lymphocyte Activation/immunology
KW - Lymphocyte Count
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Schistosoma mansoni/immunology
KW - Schistosomiasis mansoni/immunology
KW - T-Lymphocytes, Helper-Inducer/immunology
KW - Th2 Cells/immunology
UR - http://www.scopus.com/inward/record.url?scp=85131144013&partnerID=8YFLogxK
U2 - 10.4049/immunohorizons.2100071
DO - 10.4049/immunohorizons.2100071
M3 - Article
C2 - 34462311
AN - SCOPUS:85131144013
SN - 2573-7732
VL - 5
SP - 721
EP - 732
JO - ImmunoHorizons
JF - ImmunoHorizons
IS - 8
ER -