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.
Highlights
Mycoplasma gallisepticum (MG) causes severe inflammation and primarily infects trachea, lungs and air sacs in chickens [1]
MG‐infection reduced the number of C D8+ lymphocytes in thymus tissues We examined the number of CD8+ T-lymphocytes in thymus tissues to determine whether MG-infection induced depletion of CD8+ T-lymphocytes in chicken thymus
MG‐infection modulated autophagy and energy metabolism in chicken thymus We examined the expression of autophagy-related genes both at mRNA and protein level in order to determine the effect of MG-infection on autophagy
Summary
Mycoplasma gallisepticum (MG) causes severe inflammation and primarily infects trachea, lungs and air sacs in chickens [1]. The thymus is a central and primary lymphoid organ, where development, differentiation, maturation and selection of T-lymphocytes is orchestrated [9]. Thymic injury can cause serious consequences to immune development and immature immune system [10]. Accumulative evidence showed that multiple pathogens can target the thymus in mammals, resulting in functional disorder and organ atrophy [11, 12]. Pathogens including viruses, bacteria and parasites were reported to cause thymic atrophy [13]. Previous studies reported that thymus injury was commonly found during infections [11, 15], which is indirectly related to immune impairment. Studies are needed to elucidate the effect of MGinfection on thymus function in chickens
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