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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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Characterization of immune system proteins.The immune system BP was the only with significant differences between infected and uninfected animals in both young and adults and was selected for further analysis. (A) Venn diagram of immune system proteins in young and adult animals, showing the number of differentially under-represented and over-represented proteins when comparing infected (TB+) and uninfected (TB-) young animals or uninfected (TB-), infected with TB lesions localized in the head (TB+) and infected with TB lesions affecting multiple organs (TB++) adult animals. (B) Representation profile of immune system differentially represented proteins in young and adult animals.
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pntd.0004541.g004: Characterization of immune system proteins.The immune system BP was the only with significant differences between infected and uninfected animals in both young and adults and was selected for further analysis. (A) Venn diagram of immune system proteins in young and adult animals, showing the number of differentially under-represented and over-represented proteins when comparing infected (TB+) and uninfected (TB-) young animals or uninfected (TB-), infected with TB lesions localized in the head (TB+) and infected with TB lesions affecting multiple organs (TB++) adult animals. (B) Representation profile of immune system differentially represented proteins in young and adult animals.

Mentions: Of the BPs represented in young and adult wild boar, only the immune system BP was significantly different between infected and uninfected animals in both age groups (Fig 2A and 2B). Immune system proteins play an important role in host response to mycobacteria and other infectious microorganisms and were therefore selected for further analysis. A total of 27 and 31 proteins were included into the immune system BP in young and adult animals, respectively (Fig 4A). Of them, 5 and 6 proteins were differentially represented in young and adult animals, respectively (Fig 4A). In young animals, all 5 immune system proteins S100A9 (C3S7K6), uncharacterized Heme peroxidase (F1RRP1), LTF (Q6YT39), uncharacterized Cathelicidin (I3LNT1) and PGLYRP1 (F1RM24) were under-represented in TB+ animals when compared to uninfected TB- controls (Fig 4A and 4B). In adults, 3 proteins (LTF, Cathelicidin, PGLYRP1) had the same representation than in young animals while the other 3 proteins were over-represented in infected TB+ (MHC class I antigen, MHCI; Q8SPA3) or TB++ (Heme peroxidase, LTF) animals when compared to uninfected TB- controls (Fig 4A and 4B). Additionally, 5 of the differentially represented proteins in adults (S100A9, Heme peroxidase, LTF, Cathelicidin, PGLYRP1) were over-represented in TB++ when compared to TB+ animals (Fig 4A and 4B).


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)

Characterization of immune system proteins.The immune system BP was the only with significant differences between infected and uninfected animals in both young and adults and was selected for further analysis. (A) Venn diagram of immune system proteins in young and adult animals, showing the number of differentially under-represented and over-represented proteins when comparing infected (TB+) and uninfected (TB-) young animals or uninfected (TB-), infected with TB lesions localized in the head (TB+) and infected with TB lesions affecting multiple organs (TB++) adult animals. (B) Representation profile of immune system differentially represented proteins in young and adult animals.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0004541.g004: Characterization of immune system proteins.The immune system BP was the only with significant differences between infected and uninfected animals in both young and adults and was selected for further analysis. (A) Venn diagram of immune system proteins in young and adult animals, showing the number of differentially under-represented and over-represented proteins when comparing infected (TB+) and uninfected (TB-) young animals or uninfected (TB-), infected with TB lesions localized in the head (TB+) and infected with TB lesions affecting multiple organs (TB++) adult animals. (B) Representation profile of immune system differentially represented proteins in young and adult animals.
Mentions: Of the BPs represented in young and adult wild boar, only the immune system BP was significantly different between infected and uninfected animals in both age groups (Fig 2A and 2B). Immune system proteins play an important role in host response to mycobacteria and other infectious microorganisms and were therefore selected for further analysis. A total of 27 and 31 proteins were included into the immune system BP in young and adult animals, respectively (Fig 4A). Of them, 5 and 6 proteins were differentially represented in young and adult animals, respectively (Fig 4A). In young animals, all 5 immune system proteins S100A9 (C3S7K6), uncharacterized Heme peroxidase (F1RRP1), LTF (Q6YT39), uncharacterized Cathelicidin (I3LNT1) and PGLYRP1 (F1RM24) were under-represented in TB+ animals when compared to uninfected TB- controls (Fig 4A and 4B). In adults, 3 proteins (LTF, Cathelicidin, PGLYRP1) had the same representation than in young animals while the other 3 proteins were over-represented in infected TB+ (MHC class I antigen, MHCI; Q8SPA3) or TB++ (Heme peroxidase, LTF) animals when compared to uninfected TB- controls (Fig 4A and 4B). Additionally, 5 of the differentially represented proteins in adults (S100A9, Heme peroxidase, LTF, Cathelicidin, PGLYRP1) were over-represented in TB++ when compared to TB+ animals (Fig 4A and 4B).

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