Appendectomy Mitigates Coxsackievirus B3−Induced Viral Myocarditis
Appendix has a distinct abundance of lymphatic cells and serves as a reservoir of microbiota which helps to replenish the large intestine with healthy flora. And it is the primary site of IgA induction, which shapes the composition of the intestinal microbiota. Recent population-based cohort studies...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/10/1974 |
| _version_ | 1811153775224684544 |
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| author | Chengrui Niu Wei Xu Sidong Xiong |
| author_facet | Chengrui Niu Wei Xu Sidong Xiong |
| author_sort | Chengrui Niu |
| collection | DOAJ |
| description | Appendix has a distinct abundance of lymphatic cells and serves as a reservoir of microbiota which helps to replenish the large intestine with healthy flora. And it is the primary site of IgA induction, which shapes the composition of the intestinal microbiota. Recent population-based cohort studies report that appendectomy is associated with an increased risk of acute myocardial infarction and ischemic heart disease. Here, whether appendectomy has an effect on the occurrence and development of coxsackievirus B3 (CVB3)−induced viral myocarditis is studied. 10<sup>3</sup> TCID<sub>50</sub> CVB3 was inoculated i.p. into appendectomized and sham-operated mice. RNA levels of viral load and pro-inflammatory cytokines in the hearts and the intestine were detected by RT−PCR. Compared to sham-operated mice, appendectomized mice exhibited attenuated cardiac inflammation and improved cardiac function, which is associated with a systemic reduced viral load. Appendectomized mice also displayed a reduction in cardiac neutrophil and macrophage infiltration and pro-inflammatory cytokine production. Mechanistically, we found that CVB3 induced an early and potent IL-10 production in the cecal patch at 2 days post infection. Appendectomy significantly decreased intestinal IL-10 and IL-10<sup>+</sup> CD4<sup>+</sup> Treg frequency which led to a marked increase in intestinal (primary entry site for CVB3) anti-viral IFN-γ<sup>+</sup> CD4<sup>+</sup> T and IFN-γ<sup>+</sup> CD8<sup>+</sup> T response and viral restriction, eventually resulting in improved myocarditis. Our results suggest that appendix modulates cardiac infection and inflammation through regulating intestinal IL-10<sup>+</sup> Treg response. |
| first_indexed | 2024-03-10T20:49:51Z |
| format | Article |
| id | doaj.art-578963f1dc474001a741b6a3838e8bab |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T20:49:51Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-578963f1dc474001a741b6a3838e8bab2023-11-19T18:26:18ZengMDPI AGViruses1999-49152023-09-011510197410.3390/v15101974Appendectomy Mitigates Coxsackievirus B3−Induced Viral MyocarditisChengrui Niu0Wei Xu1Sidong Xiong2Jiangsu Provincial Key Laboratory of Infection and Immunity, Institute of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaJiangsu Provincial Key Laboratory of Infection and Immunity, Institute of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaJiangsu Provincial Key Laboratory of Infection and Immunity, Institute of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaAppendix has a distinct abundance of lymphatic cells and serves as a reservoir of microbiota which helps to replenish the large intestine with healthy flora. And it is the primary site of IgA induction, which shapes the composition of the intestinal microbiota. Recent population-based cohort studies report that appendectomy is associated with an increased risk of acute myocardial infarction and ischemic heart disease. Here, whether appendectomy has an effect on the occurrence and development of coxsackievirus B3 (CVB3)−induced viral myocarditis is studied. 10<sup>3</sup> TCID<sub>50</sub> CVB3 was inoculated i.p. into appendectomized and sham-operated mice. RNA levels of viral load and pro-inflammatory cytokines in the hearts and the intestine were detected by RT−PCR. Compared to sham-operated mice, appendectomized mice exhibited attenuated cardiac inflammation and improved cardiac function, which is associated with a systemic reduced viral load. Appendectomized mice also displayed a reduction in cardiac neutrophil and macrophage infiltration and pro-inflammatory cytokine production. Mechanistically, we found that CVB3 induced an early and potent IL-10 production in the cecal patch at 2 days post infection. Appendectomy significantly decreased intestinal IL-10 and IL-10<sup>+</sup> CD4<sup>+</sup> Treg frequency which led to a marked increase in intestinal (primary entry site for CVB3) anti-viral IFN-γ<sup>+</sup> CD4<sup>+</sup> T and IFN-γ<sup>+</sup> CD8<sup>+</sup> T response and viral restriction, eventually resulting in improved myocarditis. Our results suggest that appendix modulates cardiac infection and inflammation through regulating intestinal IL-10<sup>+</sup> Treg response.https://www.mdpi.com/1999-4915/15/10/1974appendectomyCVB3viral myocarditisIL-10 |
| spellingShingle | Chengrui Niu Wei Xu Sidong Xiong Appendectomy Mitigates Coxsackievirus B3−Induced Viral Myocarditis Viruses appendectomy CVB3 viral myocarditis IL-10 |
| title | Appendectomy Mitigates Coxsackievirus B3−Induced Viral Myocarditis |
| title_full | Appendectomy Mitigates Coxsackievirus B3−Induced Viral Myocarditis |
| title_fullStr | Appendectomy Mitigates Coxsackievirus B3−Induced Viral Myocarditis |
| title_full_unstemmed | Appendectomy Mitigates Coxsackievirus B3−Induced Viral Myocarditis |
| title_short | Appendectomy Mitigates Coxsackievirus B3−Induced Viral Myocarditis |
| title_sort | appendectomy mitigates coxsackievirus b3 induced viral myocarditis |
| topic | appendectomy CVB3 viral myocarditis IL-10 |
| url | https://www.mdpi.com/1999-4915/15/10/1974 |
| work_keys_str_mv | AT chengruiniu appendectomymitigatescoxsackievirusb3inducedviralmyocarditis AT weixu appendectomymitigatescoxsackievirusb3inducedviralmyocarditis AT sidongxiong appendectomymitigatescoxsackievirusb3inducedviralmyocarditis |