Related Experiment Video
Updated: Jan 16, 2026
Visualization of IL-22-expressing Lymphocytes Using Reporter Mice
Published on: January 25, 2017
Intestinal IL-22RA1 signaling regulates Chlamydia deficient in plasmid-encoded pGP3 spreading to large intestine
Qi Tian1, Guangchi Fang2, Jingyue Ma3
1Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China.
Abstract:
Chlamydia trachomatis is the most important infectious cause of tubal infertility and is frequently detected in the human gastrointestinal tract. Chlamydia muridarum, a murine pathogen, closely resembles the human pathogen C. trachomatis. Our previous studies showed that the pGP3-deficient C. muridarum mutant was restricted to the large intestine following intracolonic inoculation, suggesting that the pGP3-deficient mutant was killed by the tissue beyond the large intestine. Here, we report that the intra-ilenum, but not the intra-jejunum, to bypass the gastric barrier rescued the colonization of pGP3-deficient C. muridarum, suggesting that pGP3 is required to overcome host factors of the jejunum to help C. muridarum reach the colon. Moreover, mice genetically deficient in IL-22 not only rescued the colonization of pGP3-deficient C. muridarum following intrajejunal inoculation but also rescued the colonization of pGP3-deficient C. muridarum in the whole gastrointestinal tract tissues following intracolonic inoculation on day 14, suggesting a critical role of IL-22 in regulating chlamydial spread. Importantly, IL-22RA1 flox/flox and Villin-cre mice rescued the colonization of pGP3-deficient C. muridarum following intrajejunal inoculation, suggesting that intestinal epithelial-specific IL-22RA1 signaling is important for the spread of pGP3-deficient C. muridarum from the small intestine to the large intestine. These observations provide a platform for further research on intestinal IL-22RA1 signaling in regulating bacterial spread in the intestine. Therefore, host factors identified in the gastrointestinal tract may also contribute to the female lower genital tract barrier during sexually transmitted diseases.
Insights
Chlamydia muridarum lacking pGP3 requires jejunal host factors to colonize the large intestine. Interleukin-22 (IL-22) and its receptor IL-22RA1 on intestinal cells are crucial for controlling this chlamydial spread.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Chlamydia trachomatis causes tubal infertility and is found in the human gut.
- Chlamydia muridarum, a mouse pathogen, is similar to C. trachomatis.
- A pGP3-deficient C. muridarum mutant was previously found restricted to the large intestine.
Purpose of the Study:
- To investigate the role of pGP3 in C. muridarum colonization of the gastrointestinal tract.
- To identify host factors, specifically Interleukin-22 (IL-22), involved in regulating chlamydial spread.
- To determine the importance of intestinal epithelial IL-22 signaling in controlling C. muridarum.
Main Methods:
- Intra-ileal and intra-jejunal inoculation of pGP3-deficient C. muridarum in mice.
- Inoculation of pGP3-deficient C. muridarum in mice genetically deficient in IL-22.
- Inoculation of pGP3-deficient C. muridarum in IL-22RA1 conditional knockout mice (IL-22RA1 flox/flox and Villin-cre).
- Assessment of chlamydial colonization in gastrointestinal tract tissues.
Main Results:
- Intra-ileal, but not intra-jejunal, inoculation rescued colonization of pGP3-deficient C. muridarum, indicating jejunal host factors are involved.
- Mice lacking IL-22 showed rescued colonization of pGP3-deficient C. muridarum after intrajejunal and intracolonic inoculation.
- Conditional knockout mice lacking IL-22RA1 specifically in intestinal epithelial cells also showed rescued colonization after intrajejunal inoculation.
- These findings highlight IL-22 and intestinal epithelial IL-22RA1 signaling as critical regulators of C. muridarum spread.
Conclusions:
- pGP3 is essential for C. muridarum to overcome jejunal host defenses and colonize the large intestine.
- IL-22 plays a significant role in restricting chlamydial spread within the gastrointestinal tract.
- Intestinal epithelial IL-22RA1 signaling is vital for controlling C. muridarum dissemination from the small to the large intestine.
- Gut-associated host factors may also influence lower genital tract barriers against sexually transmitted infections.
Related Concept Videos
01:29Bacterial Phylum Chlamydiae
01:15Transcytosis of IgG
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...