Mycoplasma gallisepticum triggers immune damage in the chicken thymus by activating the TLR-2/MyD88/NF-κB signaling pathway and NLRP3 inflammasome

Abstract Previous studies reported that Mycoplasma gallisepticum (MG) causes immune dysregulation in chickens. However, the underlying mechanisms of immune dysregulation in chickens are still unclear. The thymus is a primary lymphoid organ where the proliferation, differentiation and selection of T-...

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Main Authors: Chunli Chen, Jichang Li, Wei Zhang, Syed Waqas Ali Shah, Muhammad Ishfaq
Format: Article
Language:English
Published: BMC 2020-04-01
Series:Veterinary Research
Online Access:http://link.springer.com/article/10.1186/s13567-020-00777-x
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author Chunli Chen
Jichang Li
Wei Zhang
Syed Waqas Ali Shah
Muhammad Ishfaq
author_facet Chunli Chen
Jichang Li
Wei Zhang
Syed Waqas Ali Shah
Muhammad Ishfaq
author_sort Chunli Chen
collection DOAJ
description Abstract Previous studies reported that Mycoplasma gallisepticum (MG) causes immune dysregulation in chickens. However, the underlying mechanisms of immune dysregulation in chickens are still unclear. The thymus is a primary lymphoid organ where the proliferation, differentiation and selection of T-lymphocytes occur, whereas T-lymphocytes play a crucial role in innate immune responses. To evaluate the effects of MG-infection on chicken thymus, White Leghorn chickens were divided into (1) control group and (2) MG-infection group. ATPase activities were detected by commercial kits. The hallmarks of inflammation, autophagy and energy metabolism were examined in chicken thymus tissues by histopathology, transmission electron microscopy, immunofluorescence microscopy, RT-PCR and western blotting. Immunofluorescence examination revealed that the number of CD8+ lymphocytes has significantly reduced in MG-infection group. In addition, morphological analysis revealed that MG induced inflammatory cells infiltration. The mitochondria were swollen and chromatin material was condensed in MG-infection group. The mRNA and protein expression results showed that MG-infection triggered the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome through TLR-2/MyD88/NF-κB signaling pathway. Meanwhile, the expressions of autophagy-related genes were reduced both at mRNA and protein level in MG-infection group. While, ATPase activities and the expression of energy metabolism-related genes were reduced in the thymus of MG-infected chickens. These results showed that MG-infection triggered inflammatory response through TLR-2/MyD88/NF-κB signaling pathway, activated NLRP3 inflammasome, reduced the level of autophagy and impaired energy metabolism, which then lead to tissue damage in chicken thymus. The data provide new insights in MG-infection-mediated immune damage and provide possible therapeutic targets for future targeted therapy.
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spelling doaj.art-7b5dc9f783d749b1a0b32bea036c18962022-12-22T03:01:52ZengBMCVeterinary Research1297-97162020-04-0151111310.1186/s13567-020-00777-xMycoplasma gallisepticum triggers immune damage in the chicken thymus by activating the TLR-2/MyD88/NF-κB signaling pathway and NLRP3 inflammasomeChunli Chen0Jichang Li1Wei Zhang2Syed Waqas Ali Shah3Muhammad Ishfaq4Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural UniversityHeilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural UniversityHeilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural UniversityCollege of Animal Science and Technology, Northeast Agricultural UniversityHeilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural UniversityAbstract Previous studies reported that Mycoplasma gallisepticum (MG) causes immune dysregulation in chickens. However, the underlying mechanisms of immune dysregulation in chickens are still unclear. The thymus is a primary lymphoid organ where the proliferation, differentiation and selection of T-lymphocytes occur, whereas T-lymphocytes play a crucial role in innate immune responses. To evaluate the effects of MG-infection on chicken thymus, White Leghorn chickens were divided into (1) control group and (2) MG-infection group. ATPase activities were detected by commercial kits. The hallmarks of inflammation, autophagy and energy metabolism were examined in chicken thymus tissues by histopathology, transmission electron microscopy, immunofluorescence microscopy, RT-PCR and western blotting. Immunofluorescence examination revealed that the number of CD8+ lymphocytes has significantly reduced in MG-infection group. In addition, morphological analysis revealed that MG induced inflammatory cells infiltration. The mitochondria were swollen and chromatin material was condensed in MG-infection group. The mRNA and protein expression results showed that MG-infection triggered the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome through TLR-2/MyD88/NF-κB signaling pathway. Meanwhile, the expressions of autophagy-related genes were reduced both at mRNA and protein level in MG-infection group. While, ATPase activities and the expression of energy metabolism-related genes were reduced in the thymus of MG-infected chickens. These results showed that MG-infection triggered inflammatory response through TLR-2/MyD88/NF-κB signaling pathway, activated NLRP3 inflammasome, reduced the level of autophagy and impaired energy metabolism, which then lead to tissue damage in chicken thymus. The data provide new insights in MG-infection-mediated immune damage and provide possible therapeutic targets for future targeted therapy.http://link.springer.com/article/10.1186/s13567-020-00777-x
spellingShingle Chunli Chen
Jichang Li
Wei Zhang
Syed Waqas Ali Shah
Muhammad Ishfaq
Mycoplasma gallisepticum triggers immune damage in the chicken thymus by activating the TLR-2/MyD88/NF-κB signaling pathway and NLRP3 inflammasome
Veterinary Research
title Mycoplasma gallisepticum triggers immune damage in the chicken thymus by activating the TLR-2/MyD88/NF-κB signaling pathway and NLRP3 inflammasome
title_full Mycoplasma gallisepticum triggers immune damage in the chicken thymus by activating the TLR-2/MyD88/NF-κB signaling pathway and NLRP3 inflammasome
title_fullStr Mycoplasma gallisepticum triggers immune damage in the chicken thymus by activating the TLR-2/MyD88/NF-κB signaling pathway and NLRP3 inflammasome
title_full_unstemmed Mycoplasma gallisepticum triggers immune damage in the chicken thymus by activating the TLR-2/MyD88/NF-κB signaling pathway and NLRP3 inflammasome
title_short Mycoplasma gallisepticum triggers immune damage in the chicken thymus by activating the TLR-2/MyD88/NF-κB signaling pathway and NLRP3 inflammasome
title_sort mycoplasma gallisepticum triggers immune damage in the chicken thymus by activating the tlr 2 myd88 nf κb signaling pathway and nlrp3 inflammasome
url http://link.springer.com/article/10.1186/s13567-020-00777-x
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