Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis

PLoS Negl Trop Dis. 2016 Mar 30;10(3):e0004541. doi: 10.1371/journal.pntd.0004541. eCollection 2016 Mar.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation / immunology
  • Hemoglobins / metabolism
  • Humans
  • Lymph Nodes / metabolism
  • Mycobacterium bovis*
  • Proteomics*
  • Sus scrofa
  • Swine
  • Swine Diseases / immunology*
  • Tuberculosis / immunology
  • Tuberculosis / veterinary*

Substances

  • Hemoglobins

Grants and funding

This research was supported by grants AGL2014-56305 and IPT-2011-0735-010000 from Ministerio de Economía y Competitividad, Spain, and the European Union FP7 ANTIGONE grant 278976 and Horizon 2020 COMPARE Grant 377/14. LMH was supported by a University of Castilla La Mancha (UCLM) fellowship. MV was supported by the Research Plan of UCLM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.