title: Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis.
abstract: Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to limit pathogen multiplication and promote survival, facilitating pathogen transmission.
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors.forename: Vladimir
authors.initials: V
authors.lastname: López
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Villar
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC CSIC-UCLM-JCCM, Ciudad Real, Spain.|CIBIO/InBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, Vairão, Portugal.|Departamento de Biologia, Faculdade de Ciências da Universidade do Porto (FCUP), Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Queirós
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Vicente
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Mateos-Hernández
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC CSIC-UCLM-JCCM, Ciudad Real, Spain.|Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Iratxe
authors.initials: I
authors.lastname: Díez-Delgado
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors.forename: Marinela
authors.initials: M
authors.lastname: Contreras
authors.affiliation: CIBIO/InBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, Vairão, Portugal.|Departamento de Biologia, Faculdade de Ciências da Universidade do Porto (FCUP), Porto, Portugal.|Wildlife Biology Program, University of Montana, Missoula, Montana, United States of America.
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Alves
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Alberdi
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Gortázar
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC CSIC-UCLM-JCCM, Ciudad Real, Spain.|Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, United States of America.
authors.forename: José
authors.initials: J
authors.lastname: de la Fuente
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000276:immunology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism; D009163:Mycobacterium bovis; D040901:Proteomics; D034421:Sus scrofa; D013552:Swine; D013553:Swine Diseases / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000662:veterinary*
chemical_list: D006454:Hemoglobins