The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation

M. C.C. Canesso, L. Lemos, T. C. Neves, F. M. Marim, T. B.R. Castro, És Veloso, C. P. Queiroz, Jeonghyun Ahn, H. C. Santiago, F. S. Martins, J. Alves-Silva, E. Ferreira, D. C. Cara, A. T. Vieira, Glen N Barber, S. C. Oliveira, A. M.C. Faria

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING '/' mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice. Fecal content and microbiota DNA could activate STING, indicating a role of this molecule in gut. Microbiota composition was altered in STING '/' mice toward a more inflammatory profile, evidencing a reduction in the Allobacolum and Bifidobacterium groups along with increase in Disulfovibrio bacteria. Absence of STING lead to decrease in induced intraepithelial lymphocytes (IEL) and to increase in group 1 innate lymphoid cell (ILC1) as well as ILC3 frequencies and decrease in ILC2 in the colon. Development and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING '/' mice. Moreover, these mice were highly susceptible to dextran sodium sulfate-induced colitis, T-cell-induced colitis, and enteric Salmonella typhimurium infection when compared with WT animals. Therefore, our results identify an important role of STING in maintaining gut homeostasis and also a protective effect in controlling gut inflammation.

Original languageEnglish (US)
Pages (from-to)820-834
Number of pages15
JournalMucosal Immunology
Volume11
Issue number3
DOIs
StatePublished - May 1 2018

Fingerprint

Interferons
Homeostasis
Inflammation
Genes
Microbiota
Colitis
Lymphocytes
Secretory Immunoglobulin A
Dextran Sulfate
Bifidobacterium
Wild Animals
Goblet Cells
Salmonella Infections
Regulatory T-Lymphocytes
Salmonella typhimurium
Mucus
Intestinal Mucosa
Autoimmune Diseases
Colon
Bacteria

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Canesso, M. C. C., Lemos, L., Neves, T. C., Marim, F. M., Castro, T. B. R., Veloso, É., ... Faria, A. M. C. (2018). The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation. Mucosal Immunology, 11(3), 820-834. https://doi.org/10.1038/mi.2017.88

The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation. / Canesso, M. C.C.; Lemos, L.; Neves, T. C.; Marim, F. M.; Castro, T. B.R.; Veloso, És; Queiroz, C. P.; Ahn, Jeonghyun; Santiago, H. C.; Martins, F. S.; Alves-Silva, J.; Ferreira, E.; Cara, D. C.; Vieira, A. T.; Barber, Glen N; Oliveira, S. C.; Faria, A. M.C.

In: Mucosal Immunology, Vol. 11, No. 3, 01.05.2018, p. 820-834.

Research output: Contribution to journalArticle

Canesso, MCC, Lemos, L, Neves, TC, Marim, FM, Castro, TBR, Veloso, É, Queiroz, CP, Ahn, J, Santiago, HC, Martins, FS, Alves-Silva, J, Ferreira, E, Cara, DC, Vieira, AT, Barber, GN, Oliveira, SC & Faria, AMC 2018, 'The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation', Mucosal Immunology, vol. 11, no. 3, pp. 820-834. https://doi.org/10.1038/mi.2017.88
Canesso MCC, Lemos L, Neves TC, Marim FM, Castro TBR, Veloso É et al. The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation. Mucosal Immunology. 2018 May 1;11(3):820-834. https://doi.org/10.1038/mi.2017.88
Canesso, M. C.C. ; Lemos, L. ; Neves, T. C. ; Marim, F. M. ; Castro, T. B.R. ; Veloso, És ; Queiroz, C. P. ; Ahn, Jeonghyun ; Santiago, H. C. ; Martins, F. S. ; Alves-Silva, J. ; Ferreira, E. ; Cara, D. C. ; Vieira, A. T. ; Barber, Glen N ; Oliveira, S. C. ; Faria, A. M.C. / The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation. In: Mucosal Immunology. 2018 ; Vol. 11, No. 3. pp. 820-834.
@article{5179bf354f6346cf97c4718b91aa03f3,
title = "The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation",
abstract = "STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING '/' mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice. Fecal content and microbiota DNA could activate STING, indicating a role of this molecule in gut. Microbiota composition was altered in STING '/' mice toward a more inflammatory profile, evidencing a reduction in the Allobacolum and Bifidobacterium groups along with increase in Disulfovibrio bacteria. Absence of STING lead to decrease in induced intraepithelial lymphocytes (IEL) and to increase in group 1 innate lymphoid cell (ILC1) as well as ILC3 frequencies and decrease in ILC2 in the colon. Development and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING '/' mice. Moreover, these mice were highly susceptible to dextran sodium sulfate-induced colitis, T-cell-induced colitis, and enteric Salmonella typhimurium infection when compared with WT animals. Therefore, our results identify an important role of STING in maintaining gut homeostasis and also a protective effect in controlling gut inflammation.",
author = "Canesso, {M. C.C.} and L. Lemos and Neves, {T. C.} and Marim, {F. M.} and Castro, {T. B.R.} and {\'E}s Veloso and Queiroz, {C. P.} and Jeonghyun Ahn and Santiago, {H. C.} and Martins, {F. S.} and J. Alves-Silva and E. Ferreira and Cara, {D. C.} and Vieira, {A. T.} and Barber, {Glen N} and Oliveira, {S. C.} and Faria, {A. M.C.}",
year = "2018",
month = "5",
day = "1",
doi = "10.1038/mi.2017.88",
language = "English (US)",
volume = "11",
pages = "820--834",
journal = "Mucosal Immunology",
issn = "1933-0219",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation

AU - Canesso, M. C.C.

AU - Lemos, L.

AU - Neves, T. C.

AU - Marim, F. M.

AU - Castro, T. B.R.

AU - Veloso, És

AU - Queiroz, C. P.

AU - Ahn, Jeonghyun

AU - Santiago, H. C.

AU - Martins, F. S.

AU - Alves-Silva, J.

AU - Ferreira, E.

AU - Cara, D. C.

AU - Vieira, A. T.

AU - Barber, Glen N

AU - Oliveira, S. C.

AU - Faria, A. M.C.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING '/' mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice. Fecal content and microbiota DNA could activate STING, indicating a role of this molecule in gut. Microbiota composition was altered in STING '/' mice toward a more inflammatory profile, evidencing a reduction in the Allobacolum and Bifidobacterium groups along with increase in Disulfovibrio bacteria. Absence of STING lead to decrease in induced intraepithelial lymphocytes (IEL) and to increase in group 1 innate lymphoid cell (ILC1) as well as ILC3 frequencies and decrease in ILC2 in the colon. Development and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING '/' mice. Moreover, these mice were highly susceptible to dextran sodium sulfate-induced colitis, T-cell-induced colitis, and enteric Salmonella typhimurium infection when compared with WT animals. Therefore, our results identify an important role of STING in maintaining gut homeostasis and also a protective effect in controlling gut inflammation.

AB - STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING '/' mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice. Fecal content and microbiota DNA could activate STING, indicating a role of this molecule in gut. Microbiota composition was altered in STING '/' mice toward a more inflammatory profile, evidencing a reduction in the Allobacolum and Bifidobacterium groups along with increase in Disulfovibrio bacteria. Absence of STING lead to decrease in induced intraepithelial lymphocytes (IEL) and to increase in group 1 innate lymphoid cell (ILC1) as well as ILC3 frequencies and decrease in ILC2 in the colon. Development and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING '/' mice. Moreover, these mice were highly susceptible to dextran sodium sulfate-induced colitis, T-cell-induced colitis, and enteric Salmonella typhimurium infection when compared with WT animals. Therefore, our results identify an important role of STING in maintaining gut homeostasis and also a protective effect in controlling gut inflammation.

UR - http://www.scopus.com/inward/record.url?scp=85047967039&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047967039&partnerID=8YFLogxK

U2 - 10.1038/mi.2017.88

DO - 10.1038/mi.2017.88

M3 - Article

C2 - 29346345

AN - SCOPUS:85047967039

VL - 11

SP - 820

EP - 834

JO - Mucosal Immunology

JF - Mucosal Immunology

SN - 1933-0219

IS - 3

ER -