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

López V, Villar M, Queirós J, Vicente J, Mateos-Hernández L, Díez-Delgado I, Contreras M, Alves PC, Alberdi P, Gortázar C, de la Fuente J - PLoS Negl Trop Dis (2016)

Bottom Line: The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood.MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls.However, as infection progresses, wild boar immune response recovers to limit pathogen multiplication and promote survival, facilitating pathogen transmission.

View Article: PubMed Central - PubMed

Affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC CSIC-UCLM-JCCM, Ciudad Real, Spain.

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.

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Host-mycobacteria interactions.Summary of the factors identified in this study with an impact on host-pathogen interactions. Mycobacteria manipulate 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. Increased host survival in adult animals is probably associated with reduction in anemia progression. The upregulation of C3 may be associated with protection in uninfected adult wild boar while higher lesion score in TB++ animals could be due to infection with M. bovis spoligotypes such as SB0134.
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pntd.0004541.g008: Host-mycobacteria interactions.Summary of the factors identified in this study with an impact on host-pathogen interactions. Mycobacteria manipulate 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. Increased host survival in adult animals is probably associated with reduction in anemia progression. The upregulation of C3 may be associated with protection in uninfected adult wild boar while higher lesion score in TB++ animals could be due to infection with M. bovis spoligotypes such as SB0134.

Mentions: The results reported here suggested that M. bovis manipulates host immune response to facilitate infection in wild boar (Fig 8). As other intracellular bacteria, M. bovis manipulate host immune response by reducing the production of immune system proteins [26]. However, as infection progresses, wild boar immune response recover to limit pathogen multiplication and promote survival that also facilitates pathogen transmission (Fig 8). Adult TB++ wild boar with disseminated disease showed extensive macroscopic lesions with poor fibrotic containment of the granulomas and ulceration into the lumina of airways that facilitate pathogen transmission through aerogenous shedding of mycobacteria [13,42]. As previously reported for other obligate intracellular bacteria [43], host-mycobacteria interactions probably reflect a co-evolutionary process in which pathogens evolved mechanisms to subvert host response to establish infection but hosts also evolved mechanisms to limit pathogen infection and promote survival. Subsequently, mycobacteria benefit from host survival by increasing the probability for transmission to continue the life cycle. The reduction in anemia progression from TB+ to TB++ adult animals is probably associated with the increase in host survival (Fig 8).


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

López V, Villar M, Queirós J, Vicente J, Mateos-Hernández L, Díez-Delgado I, Contreras M, Alves PC, Alberdi P, Gortázar C, de la Fuente J - PLoS Negl Trop Dis (2016)

Host-mycobacteria interactions.Summary of the factors identified in this study with an impact on host-pathogen interactions. Mycobacteria manipulate 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. Increased host survival in adult animals is probably associated with reduction in anemia progression. The upregulation of C3 may be associated with protection in uninfected adult wild boar while higher lesion score in TB++ animals could be due to infection with M. bovis spoligotypes such as SB0134.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814110&req=5

pntd.0004541.g008: Host-mycobacteria interactions.Summary of the factors identified in this study with an impact on host-pathogen interactions. Mycobacteria manipulate 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. Increased host survival in adult animals is probably associated with reduction in anemia progression. The upregulation of C3 may be associated with protection in uninfected adult wild boar while higher lesion score in TB++ animals could be due to infection with M. bovis spoligotypes such as SB0134.
Mentions: The results reported here suggested that M. bovis manipulates host immune response to facilitate infection in wild boar (Fig 8). As other intracellular bacteria, M. bovis manipulate host immune response by reducing the production of immune system proteins [26]. However, as infection progresses, wild boar immune response recover to limit pathogen multiplication and promote survival that also facilitates pathogen transmission (Fig 8). Adult TB++ wild boar with disseminated disease showed extensive macroscopic lesions with poor fibrotic containment of the granulomas and ulceration into the lumina of airways that facilitate pathogen transmission through aerogenous shedding of mycobacteria [13,42]. As previously reported for other obligate intracellular bacteria [43], host-mycobacteria interactions probably reflect a co-evolutionary process in which pathogens evolved mechanisms to subvert host response to establish infection but hosts also evolved mechanisms to limit pathogen infection and promote survival. Subsequently, mycobacteria benefit from host survival by increasing the probability for transmission to continue the life cycle. The reduction in anemia progression from TB+ to TB++ adult animals is probably associated with the increase in host survival (Fig 8).

Bottom Line: The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood.MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls.However, as infection progresses, wild boar immune response recovers to limit pathogen multiplication and promote survival, facilitating pathogen transmission.

View Article: PubMed Central - PubMed

Affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC CSIC-UCLM-JCCM, Ciudad Real, Spain.

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.

Show MeSH
Related in: MedlinePlus