Skip to main content

Type I interferon signaling restrains IL-10R+ colonic macrophages and dendritic cells and leads to more severe Salmonella colitis.

Publication ,  Journal Article
Stefan, KL; Fink, A; Surana, NK; Kasper, DL; Dasgupta, S
Published in: PLoS One
2017

Type I interferons (IFNα, IFNβ) are key regulators of innate and adaptive immunity, modulating the severity of both viral and bacterial infections. While type I IFN signaling leads to improved outcomes in viral infections, its role in bacterial infections is more contextual and depends on the specific pathogen and route of infection. Given the limited evidence on whether type I IFN signaling affects enteric bacterial pathogens, we investigated the role of this signaling pathway in Salmonella enterica serovar Typhimurium (S. typhimurium)-induced colitis. Comparing mice deficient in IFNAR1- the common receptor for IFNα and IFNβ- with wild-type mice, we found that type I IFN signaling leads to more rapid death, more severe colonic inflammation, higher serum levels of pro-inflammatory cytokines, and greater bacterial dissemination. Specific ablation of plasmacytoid dendritic cells (pDCs), which are prominent producers of type I IFNs in antiviral responses, did not alter survival after infection. This result established that pDCs do not play a major role in the pathogenesis of S. typhimurium colitis. Flow cytometric analysis of macrophages and conventional dendritic cells (cDCs) during active colitis demonstrated an increase in CD11c- macrophages and CD103+ cDCs in the colon of Ifnar1-/- animals. Interestingly, cells expressing the anti-inflammatory cytokine receptor IL-10R are more abundant within these subsets in Ifnar1-/- than in wild-type mice. Moreover, blockade of IL-10R in Ifnar1-/- mice increased their susceptibility to S. typhimurium colitis, suggesting that altered numbers of these immunoregulatory cells may underlie the difference in disease severity. This cross-talk between type I IFN and IL-10R signaling pathways may represent a key host cellular mechanism to investigate further in order to unravel the balance between pathogenic inflammation and homeostasis of the colon. Taken together, our data clearly demonstrate that type I IFN signaling is pathogenic in S. typhimurium colitis.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2017

Volume

12

Issue

11

Start / End Page

e0188600

Location

United States

Related Subject Headings

  • Signal Transduction
  • Severity of Illness Index
  • Salmonella typhimurium
  • Salmonella Infections
  • Receptors, Interleukin-10
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Macrophages
  • Intestinal Mucosa
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Stefan, K. L., Fink, A., Surana, N. K., Kasper, D. L., & Dasgupta, S. (2017). Type I interferon signaling restrains IL-10R+ colonic macrophages and dendritic cells and leads to more severe Salmonella colitis. PLoS One, 12(11), e0188600. https://doi.org/10.1371/journal.pone.0188600
Stefan, Kailyn L., Avner Fink, Neeraj K. Surana, Dennis L. Kasper, and Suryasarathi Dasgupta. “Type I interferon signaling restrains IL-10R+ colonic macrophages and dendritic cells and leads to more severe Salmonella colitis.PLoS One 12, no. 11 (2017): e0188600. https://doi.org/10.1371/journal.pone.0188600.
Stefan, Kailyn L., et al. “Type I interferon signaling restrains IL-10R+ colonic macrophages and dendritic cells and leads to more severe Salmonella colitis.PLoS One, vol. 12, no. 11, 2017, p. e0188600. Pubmed, doi:10.1371/journal.pone.0188600.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2017

Volume

12

Issue

11

Start / End Page

e0188600

Location

United States

Related Subject Headings

  • Signal Transduction
  • Severity of Illness Index
  • Salmonella typhimurium
  • Salmonella Infections
  • Receptors, Interleukin-10
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Macrophages
  • Intestinal Mucosa