IL-33/ST2 Axis Plays a Protective Effect in <i>Streptococcus pyogenes</i> Infection through Strengthening of the Innate Immunity
Group A <i>Streptococcus</i> (GAS) causes invasive human diseases with the cytokine storm. Interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) axis is known to drive T<sub>H</sub>2 response, while its effect on GAS infection is unclear. We used an air pouch model to...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10566 |
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| author | Chih-Feng Kuo Wei-Yu Chen Hai-Han Yu Yu-Hsuan Tsai Ya-Chu Chang Chih-Peng Chang Nina Tsao |
| author_facet | Chih-Feng Kuo Wei-Yu Chen Hai-Han Yu Yu-Hsuan Tsai Ya-Chu Chang Chih-Peng Chang Nina Tsao |
| author_sort | Chih-Feng Kuo |
| collection | DOAJ |
| description | Group A <i>Streptococcus</i> (GAS) causes invasive human diseases with the cytokine storm. Interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) axis is known to drive T<sub>H</sub>2 response, while its effect on GAS infection is unclear. We used an air pouch model to examine the effect of the IL-33/ST2 axis on GAS-induced necrotizing fasciitis. GAS infection induced IL-33 expression in wild-type (WT) C57BL/6 mice, whereas the <i>IL</i>-<i>33</i>- and <i>ST2</i>-knockout mice had higher mortality rates, more severe skin lesions and higher bacterial loads in the air pouches than those of WT mice after infection. Surveys of infiltrating cells in the air pouch of GAS-infected mice at the early stage found that the number and cell viability of infiltrating cells in both gene knockout mice were lower than those of WT mice. The predominant effector cells in GAS-infected air pouches were neutrophils. Absence of the IL-33/ST2 axis enhanced the expression of inflammatory cytokines, but not T<sub>H</sub>1 or T<sub>H</sub>2 cytokines, in the air pouch after infection. Using in vitro assays, we found that the IL-33/ST2 axis not only enhanced neutrophil migration but also strengthened the bactericidal activity of both sera and neutrophils. These results suggest that the IL-33/ST2 axis provided the protective effect on GAS infection through enhancing the innate immunity. |
| first_indexed | 2024-03-10T07:00:23Z |
| format | Article |
| id | doaj.art-efb003796c6347d7829b5f403dea02ee |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:00:23Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-efb003796c6347d7829b5f403dea02ee2023-11-22T16:11:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191056610.3390/ijms221910566IL-33/ST2 Axis Plays a Protective Effect in <i>Streptococcus pyogenes</i> Infection through Strengthening of the Innate ImmunityChih-Feng Kuo0Wei-Yu Chen1Hai-Han Yu2Yu-Hsuan Tsai3Ya-Chu Chang4Chih-Peng Chang5Nina Tsao6School of Medicine, I-Shou University, Kaohsiung City 824005, TaiwanInstitute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City 833401, TaiwanDepartment of Biological Science and Technology, College of Medical Science and Technology, I-Shou University, Kaohsiung City 824005, TaiwanDepartment of Biological Science and Technology, College of Medical Science and Technology, I-Shou University, Kaohsiung City 824005, TaiwanDepartment of Medical Laboratory Science, College of Medical Science and Technology, I-Shou University, Kaohsiung City 824005, TaiwanDepartment of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanDepartment of Biological Science and Technology, College of Medical Science and Technology, I-Shou University, Kaohsiung City 824005, TaiwanGroup A <i>Streptococcus</i> (GAS) causes invasive human diseases with the cytokine storm. Interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) axis is known to drive T<sub>H</sub>2 response, while its effect on GAS infection is unclear. We used an air pouch model to examine the effect of the IL-33/ST2 axis on GAS-induced necrotizing fasciitis. GAS infection induced IL-33 expression in wild-type (WT) C57BL/6 mice, whereas the <i>IL</i>-<i>33</i>- and <i>ST2</i>-knockout mice had higher mortality rates, more severe skin lesions and higher bacterial loads in the air pouches than those of WT mice after infection. Surveys of infiltrating cells in the air pouch of GAS-infected mice at the early stage found that the number and cell viability of infiltrating cells in both gene knockout mice were lower than those of WT mice. The predominant effector cells in GAS-infected air pouches were neutrophils. Absence of the IL-33/ST2 axis enhanced the expression of inflammatory cytokines, but not T<sub>H</sub>1 or T<sub>H</sub>2 cytokines, in the air pouch after infection. Using in vitro assays, we found that the IL-33/ST2 axis not only enhanced neutrophil migration but also strengthened the bactericidal activity of both sera and neutrophils. These results suggest that the IL-33/ST2 axis provided the protective effect on GAS infection through enhancing the innate immunity.https://www.mdpi.com/1422-0067/22/19/10566interleukin-33 (IL-33)suppression of tumorigenicity 2 (ST2)Group A <i>Streptococcus</i> (GAS)the innate immunity |
| spellingShingle | Chih-Feng Kuo Wei-Yu Chen Hai-Han Yu Yu-Hsuan Tsai Ya-Chu Chang Chih-Peng Chang Nina Tsao IL-33/ST2 Axis Plays a Protective Effect in <i>Streptococcus pyogenes</i> Infection through Strengthening of the Innate Immunity International Journal of Molecular Sciences interleukin-33 (IL-33) suppression of tumorigenicity 2 (ST2) Group A <i>Streptococcus</i> (GAS) the innate immunity |
| title | IL-33/ST2 Axis Plays a Protective Effect in <i>Streptococcus pyogenes</i> Infection through Strengthening of the Innate Immunity |
| title_full | IL-33/ST2 Axis Plays a Protective Effect in <i>Streptococcus pyogenes</i> Infection through Strengthening of the Innate Immunity |
| title_fullStr | IL-33/ST2 Axis Plays a Protective Effect in <i>Streptococcus pyogenes</i> Infection through Strengthening of the Innate Immunity |
| title_full_unstemmed | IL-33/ST2 Axis Plays a Protective Effect in <i>Streptococcus pyogenes</i> Infection through Strengthening of the Innate Immunity |
| title_short | IL-33/ST2 Axis Plays a Protective Effect in <i>Streptococcus pyogenes</i> Infection through Strengthening of the Innate Immunity |
| title_sort | il 33 st2 axis plays a protective effect in i streptococcus pyogenes i infection through strengthening of the innate immunity |
| topic | interleukin-33 (IL-33) suppression of tumorigenicity 2 (ST2) Group A <i>Streptococcus</i> (GAS) the innate immunity |
| url | https://www.mdpi.com/1422-0067/22/19/10566 |
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