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Distinct DC subsets regulate adaptive Th1 and 2 responses during Trichuris muris infection

Demiri, M. LU ; Müller-Luda, K. LU ; Agace, W. W. LU and Svensson-Frej, M. LU (2017) In Parasite Immunology 39(10).
Abstract

Low- and high-dose infections with the murine large intestinal nematode Trichuris muris are associated with induction of adaptive Th1 and Th2 responses, respectively, in mesenteric lymph nodes (MLN). Classical dendritic cells (cDC) accumulate in the large intestinal mucosa and MLN upon T. muris infection, yet their role in driving adaptive responses to infection remains largely unknown. We performed low- and high-dose T. muris infections of mice deficient in defined cDC subsets to investigate their role in induction of adaptive immune responses. Mice lacking IRF4-dependent cDC failed to clear a high-dose infection and displayed impaired Th2 responses. Conversely, mice lacking IRF8-dependent cDC cleared a low-dose infection and displayed... (More)

Low- and high-dose infections with the murine large intestinal nematode Trichuris muris are associated with induction of adaptive Th1 and Th2 responses, respectively, in mesenteric lymph nodes (MLN). Classical dendritic cells (cDC) accumulate in the large intestinal mucosa and MLN upon T. muris infection, yet their role in driving adaptive responses to infection remains largely unknown. We performed low- and high-dose T. muris infections of mice deficient in defined cDC subsets to investigate their role in induction of adaptive immune responses. Mice lacking IRF4-dependent cDC failed to clear a high-dose infection and displayed impaired Th2 responses. Conversely, mice lacking IRF8-dependent cDC cleared a low-dose infection and displayed an impaired Th1 response while increased production of Th2 cytokines. Finally, mice lacking both IRF4- and IRF8-dependent cDC were able to generate a Th2 response and clear a low-dose infection. Collectively, these results suggest that IRF4- and IRF8-dependent cDC act antagonistically during T. muris infection, and demonstrate that intestinal Th2 responses can be generated towards T. muris in the absence of IRF4-dependent cDC.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
dendritic cells, infection, intestine, mesenteric lymph nodes, parasite, T helper cells
in
Parasite Immunology
volume
39
issue
10
publisher
Wiley-Blackwell
external identifiers
  • scopus:85029621295
  • wos:000411346100003
ISSN
0141-9838
DOI
10.1111/pim.12458
language
English
LU publication?
yes
id
60dc7813-1c2c-4574-82b4-d26a47ad5890
date added to LUP
2017-09-29 08:44:04
date last changed
2018-05-06 04:37:03
@article{60dc7813-1c2c-4574-82b4-d26a47ad5890,
  abstract     = {<p>Low- and high-dose infections with the murine large intestinal nematode Trichuris muris are associated with induction of adaptive Th1 and Th2 responses, respectively, in mesenteric lymph nodes (MLN). Classical dendritic cells (cDC) accumulate in the large intestinal mucosa and MLN upon T. muris infection, yet their role in driving adaptive responses to infection remains largely unknown. We performed low- and high-dose T. muris infections of mice deficient in defined cDC subsets to investigate their role in induction of adaptive immune responses. Mice lacking IRF4-dependent cDC failed to clear a high-dose infection and displayed impaired Th2 responses. Conversely, mice lacking IRF8-dependent cDC cleared a low-dose infection and displayed an impaired Th1 response while increased production of Th2 cytokines. Finally, mice lacking both IRF4- and IRF8-dependent cDC were able to generate a Th2 response and clear a low-dose infection. Collectively, these results suggest that IRF4- and IRF8-dependent cDC act antagonistically during T. muris infection, and demonstrate that intestinal Th2 responses can be generated towards T. muris in the absence of IRF4-dependent cDC.</p>},
  articleno    = {e12458},
  author       = {Demiri, M. and Müller-Luda, K. and Agace, W. W. and Svensson-Frej, M.},
  issn         = {0141-9838},
  keyword      = {dendritic cells,infection,intestine,mesenteric lymph nodes,parasite,T helper cells},
  language     = {eng},
  month        = {10},
  number       = {10},
  publisher    = {Wiley-Blackwell},
  series       = {Parasite Immunology},
  title        = {Distinct DC subsets regulate adaptive Th1 and 2 responses during Trichuris muris infection},
  url          = {http://dx.doi.org/10.1111/pim.12458},
  volume       = {39},
  year         = {2017},
}