Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway.
To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ) expression in int...
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2014
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oai:doaj.org-article:719b25472c0349cc8db7b99bc10a3ec62021-11-18T06:07:04ZAbsence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway.1553-73661553-737410.1371/journal.ppat.1003887https://doaj.org/article/719b25472c0349cc8db7b99bc10a3ec62014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24465207/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ) expression in intestinal epithelial cells. Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2). Accumulation of Lcn2 stabilizes the metalloproteinase MMP-9 via extracellular binding, which further aggravates the colitis. Remarkably, when exposed to S. Typhimurium, Lcn2-null mice exhibited a drastic reduction of the colitis and remained protected even at later stages of infection. Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion.Parag KunduTeo Wei LingAgata KoreckaYinghui LiRossana D'ArienzoRalph M BunteThorsten BergerVelmurugesan ArulampalamPierre ChambonTak Wah MakWalter WahliSven PetterssonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 1, p e1003887 (2014) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Parag Kundu Teo Wei Ling Agata Korecka Yinghui Li Rossana D'Arienzo Ralph M Bunte Thorsten Berger Velmurugesan Arulampalam Pierre Chambon Tak Wah Mak Walter Wahli Sven Pettersson Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway. |
| description |
To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ) expression in intestinal epithelial cells. Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2). Accumulation of Lcn2 stabilizes the metalloproteinase MMP-9 via extracellular binding, which further aggravates the colitis. Remarkably, when exposed to S. Typhimurium, Lcn2-null mice exhibited a drastic reduction of the colitis and remained protected even at later stages of infection. Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion. |
| format |
article |
| author |
Parag Kundu Teo Wei Ling Agata Korecka Yinghui Li Rossana D'Arienzo Ralph M Bunte Thorsten Berger Velmurugesan Arulampalam Pierre Chambon Tak Wah Mak Walter Wahli Sven Pettersson |
| author_facet |
Parag Kundu Teo Wei Ling Agata Korecka Yinghui Li Rossana D'Arienzo Ralph M Bunte Thorsten Berger Velmurugesan Arulampalam Pierre Chambon Tak Wah Mak Walter Wahli Sven Pettersson |
| author_sort |
Parag Kundu |
| title |
Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway. |
| title_short |
Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway. |
| title_full |
Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway. |
| title_fullStr |
Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway. |
| title_full_unstemmed |
Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway. |
| title_sort |
absence of intestinal pparγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/719b25472c0349cc8db7b99bc10a3ec6 |
| work_keys_str_mv |
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