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Ichiaki Ito, Makiko Kobayashi, Celeste C Finnerty, David N Herndon, Fujio Suzuki, Control of gut bacteria-associated sepsis by an inhibitor of group 2 innate lymphoid cells in severely burned mice, The Journal of Immunology, Volume 198, Issue Supplement_1, May 2017, Page 131.14, https://doi.org/10.4049/jimmunol.198.Supp.131.14
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Abstract
The effect of SR3335 on infectious complications caused by enterococcal translocation was studied in severely burned mice. SR3335 is an RORα selective inverse agonist for group 2 innate lymphoid cells (ILC2). Sepsis caused by Enterococcus faecalis oral infection (106 CFU/mouse) was developed in decontaminated and proton pump inhibitor treated mice subjected to burn injuries (25%TBSA burn), as previously described. These mice were treated i.p. with 100 μg/mouse of SR3335 once daily for 3 days started 1 h after burn injury. SR3335 inhibits the maturation of ILC2 through the suppression of the RORα transcriptional activity. ILC2 were isolated form the intestines and analyzed by flow cytometry. The severity of infection was evaluated by mortality and bacterial growth in organs of these mice, as previously described. In the results, all severely burned mice died within 6 days of E. faecalis oral infection, while 100% of the same mice treated with SR3335 survived more than 10 days after the infection. E. faecalis grew seriously in the organs of burned mice after the infection, but the pathogen did not grow in burned mice treated with SR3335. The increased number of ILC2 and their cytokine products (IL-5 and IL-13) were detected in the lamina propria of mice 1 to 7 days after severe burn injury. However, the number of ILC2 was not increased in the lamina propria of burned mice treated with SR3335. SCIDbg mice resisted E. faecalis oral infection, while the same mice adoptively transferred with ILC2 were shown to be susceptible to the infection. These results indicate that ILC2 play a role in the severity of gut bacteria-associated sepsis, and the ILC2 inhibitor (SR3335) is suggested to be protective against these infections in severely burned mice.
