Calves Infected with Virulent and Attenuated Mycoplasma bovis Strains Have Upregulated Th17 Inflammatory and Th1 Protective Responses, Respectively.

Chao Chao,Zhu Zhu,Li Li,Khan Khan,Lu Lu,Peng Peng,Han Han,Liu Liu,Guo Guo,Chen Chen,Hu Hu,Dong Dong

doi:10.3390/genes10090656

Abstract

Mycoplasma bovis is a critical bovine pathogen, but its pathogenesis remains poorly understood. Here, the virulent HB0801 (P1) and attenuated HB0801-P150 (P150) strains of M. bovis were used to explore the potential pathogenesis and effect of induced immunity from calves’ differential transcriptomes post infection. Nine one-month-old male calves were infected with P1, P150, or mock-infected with medium and euthanized at 60 days post-infection. Calves in P1 group exhibited other clinical signs and pathological changes compared to the other two groups. Transcriptome profiles of peripheral blood mononuclear cells revealed seven and 10 hub differentially expressed genes (DEGs) in P1 and P150 groups compared with mock-infected group, respectively. Then, P1-induced pathogenesis was predicted to be associated with enhanced Th17, and P150-induced immunity with Th1 response and expression of ubiquitination-associated enzymes. Association analysis showed that 14 and 11 DEGs were positively and negatively correlated with pathological changes, respectively. Furthermore, up-regulated expression in molecules critical to differentiation of pathogenic Th17 cells in lung and peripheral blood mononuclear cells in P1 group was validated at RNA and protein levels. The results confirmed virulent and attenuated strains might be associated with biased differentiation of pro-inflammatory pathogenic Th17 and Th1 subsets respectively.

Highlights

Mycoplasmas are the smallest self-replicating and cell wall-less organisms
Apart from clinical signs, the pathological observation at necropsy indicated the significant difference in virulence of these two strains on calves—pneumonia with the features of lung consolidation, significantly damaged alveolar architecture, lymphohistiocytic infiltrates, and exudates in bronchiolar induced by P1, which is similar to the feature of moderate M. bovis pneumonia in natural infection, while in P150 group, similar to NC group, the intact alveolar and bronchial structures were observed
These indicated that the infection was successful which laid the foundation for the further study on interaction between differentially expressed genes (DEGs) and the clinical signs, or pathological changes of calves responding to M. bovis strains

Summary

Introduction

Mycoplasma bovis is an important pathogen infecting bovines worldwide by primarily causing pneumonia, as well as other disorders such as mastitis, arthritis, and otitis. Some characteristics related to the pathogenesis of M. bovis were confirmed in vivo, such as colonizing the mucosal surfaces, invading tissues, persisting at the site of infection [1], inhibiting the respiratory burst of neutrophils [2,3], Genes 2019, 10, 656; doi:10.3390/genes10090656 www.mdpi.com/journal/genes. Some controversial conclusions remain on whether M. bovis induces apoptosis in bovine monocytes, lymphocytes, and neutrophils in vitro [7,8,9]. Despite these advances in the understanding of M. bovis pathogenesis, important knowledge gaps remain

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