Lactococcus lactis engineered to deliver hCAP18 cDNA alleviates DNBS-induced colitis in C57BL/6 mice by promoting IL17A and IL10 cytokine expression.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 09 2022
19 09 2022
Historique:
received:
17
03
2022
accepted:
30
08
2022
entrez:
19
9
2022
pubmed:
20
9
2022
medline:
23
9
2022
Statut:
epublish
Résumé
With its antimicrobial and immunomodulating properties, the cathelicidin (LL37) plays an important role in innate immune system. Here, we attempted to alleviate chemically induced colitis using a lactococci strain that either directly expressed the precursor to LL37, hCAP18 (LL-pSEC:hCAP18), or delivered hCAP18 cDNA to host cells under the control of the cytomegalovirus promoter (LL-Probi-H1:hCAP18). We also investigated whether the alleviation of symptoms could be explained through modification of the gut microbiota by hCAP18. Mice were administered daily doses of LL-pSEC:hCAP18 or LL-Probi-H1:hCAP18. On day 7, colitis was induced by DNBS. During autopsy, we assessed macroscopic tissue damage in the colon and collected tissue samples for the characterization of inflammation markers and histological analysis. Feces were collected at day 7 for 16S DNA sequencing. We also performed a fecal transplant experiment in which mice underwent colon washing and received feces from Lactococcus lactis-treated mice before DNBS-colitis induction. Treatment with LL-Probi-H1:hCAP18 reduced the severity of colitis symptoms. The protective effects were accompanied by increased levels of IL17A and IL10 in mesenteric lymph node cells. L. lactis administration altered the abundance of Lachnospiraceae and Muribaculaceae. However, fecal transplant from L. lactis-treated mice did not improve DNBS-induced symptoms in recipient mice.
Identifiants
pubmed: 36123355
doi: 10.1038/s41598-022-19455-3
pii: 10.1038/s41598-022-19455-3
pmc: PMC9485145
doi:
Substances chimiques
CAMP protein, human
0
Cathelicidins
0
Cytokines
0
DNA, Complementary
0
Il17a protein, mouse
0
Interleukin-17
0
Interleukin-10
130068-27-8
2,4-dinitrofluorobenzene sulfonic acid
143134-35-4
Dinitrofluorobenzene
D241E059U6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15641Informations de copyright
© 2022. The Author(s).
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