Early diagnosis, genomic resistance to bovine paratuberculosis, and regulation of the host response against this infection

• Autores: Gerard Badia Bringué
• Directores de la Tesis: Begoña Marina Jugo Orrantia (dir. tes.), Marta Alonso Hearn (dir. tes.)
• Lectura: En la Universidad del País Vasco - Euskal Herriko Unibertsitatea ( España ) en 2025
• Idioma: inglés
• Número de páginas: 350
• Enlaces
  • Tesis en acceso abierto en: ADDI
• Resumen

  • Bovine paratuberculosis (PTB) is an infectious chronic disease caused by Mycobacterium avium subsp.paratuberculosis (MAP), which affects ruminants worldwide and is a burden on the dairy industry. Thedetection of subclinical infections remains a challenge, and novel tools are needed to detect MAPinfectedanimals at the subclinical stages of the disease. In the first publication of this thesis, a dropletdigital polymerase chain reaction (ddPCR) assay to detect and quantify a fragment of the F57 MAPspecificsequence in samples of naturally MAP-infected Holstein cattle was designed. The blood ddPCRwas the most sensitive tool of all the quantitative methods used in the study for the detection ofsubclinical cows with focal lesions. In the second and third studies of this thesis, RNA sequencing wasused to compare the expression of miRNAs and alternative splicing (AS) events in ileocecal valve (ICV)and peripheral blood (PB) samples of Holstein cows with focal or diffuse PTB-associated lesions in guttissues versus control cows without lesions. Aside from the utility of miRNAs and AS events asbiomarkers for the detection of subclinical MAP infection, the analysis of miRNAs expression andsplicing patterns allowed a better understanding of the regulatory mechanisms of the host responseagainst MAP infection at the transcriptomic level. Single nucleotide polymorphisms (SNPs) can alsoregulate host immune response and therefore specific PTB outcomes. In the fourth study of this thesis,two novel cis-eQTLs were identified as pleiotropically associated with the expression of EGR4 andMGC134040 and the presence of multifocal and diffuse lesions, respectively. In the fifth and sixth studiesincluded in this thesis, we define two heritable and distinct immunogenetic profiles associated with thecapability of MAP-infected macrophages to limit bacterial load and to produce high IFN-¿ levels earlyafter infection. These results open the possibility of ranking and selecting Holstein cattle based on theirimmunocompetence, ultimately reducing PTB prevalence, preventing economic losses, extending cattle¿sproductive life and improving food safety.