Genome-wide screen for Mycobacterium tuberculosis genes that regulate host immunity.
In spite of its highly immunogenic properties, Mycobacterium tuberculosis (Mtb) establishes persistent infection in otherwise healthy individuals, making it one of the most widespread and deadly human pathogens. Mtb's prolonged survival may reflect production of microbial factors that prevent e...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-12-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3000826?pdf=render |
| _version_ | 1818129320427651072 |
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| author | Aimee M Beaulieu Poonam Rath Marianne Imhof Mark E Siddall Julia Roberts Dirk Schnappinger Carl F Nathan |
| author_facet | Aimee M Beaulieu Poonam Rath Marianne Imhof Mark E Siddall Julia Roberts Dirk Schnappinger Carl F Nathan |
| author_sort | Aimee M Beaulieu |
| collection | DOAJ |
| description | In spite of its highly immunogenic properties, Mycobacterium tuberculosis (Mtb) establishes persistent infection in otherwise healthy individuals, making it one of the most widespread and deadly human pathogens. Mtb's prolonged survival may reflect production of microbial factors that prevent even more vigorous immunity (quantitative effect) or that divert the immune response to a non-sterilizing mode (qualitative effect). Disruption of Mtb genes has produced a list of several dozen candidate immunomodulatory factors. Here we used robotic fluorescence microscopy to screen 10,100 loss-of-function transposon mutants of Mtb for their impact on the expression of promoter-reporter constructs for 12 host immune response genes in a mouse macrophage cell line. The screen identified 364 candidate immunoregulatory genes. To illustrate the utility of the candidate list, we confirmed the impact of 35 Mtb mutant strains on expression of endogenous immune response genes in primary macrophages. Detailed analysis focused on a strain of Mtb in which a transposon disrupts Rv0431, a gene encoding a conserved protein of unknown function. This mutant elicited much more macrophage TNFα, IL-12p40 and IL-6 in vitro than wild type Mtb, and was attenuated in the mouse. The mutant list provides a platform for exploring the immunobiology of tuberculosis, for example, by combining immunoregulatory mutations in a candidate vaccine strain. |
| first_indexed | 2024-12-11T07:47:16Z |
| format | Article |
| id | doaj.art-928683ad08f44e719a5cf82b82d7400c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T07:47:16Z |
| publishDate | 2010-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-928683ad08f44e719a5cf82b82d7400c2022-12-22T01:15:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-12-01512e1512010.1371/journal.pone.0015120Genome-wide screen for Mycobacterium tuberculosis genes that regulate host immunity.Aimee M BeaulieuPoonam RathMarianne ImhofMark E SiddallJulia RobertsDirk SchnappingerCarl F NathanIn spite of its highly immunogenic properties, Mycobacterium tuberculosis (Mtb) establishes persistent infection in otherwise healthy individuals, making it one of the most widespread and deadly human pathogens. Mtb's prolonged survival may reflect production of microbial factors that prevent even more vigorous immunity (quantitative effect) or that divert the immune response to a non-sterilizing mode (qualitative effect). Disruption of Mtb genes has produced a list of several dozen candidate immunomodulatory factors. Here we used robotic fluorescence microscopy to screen 10,100 loss-of-function transposon mutants of Mtb for their impact on the expression of promoter-reporter constructs for 12 host immune response genes in a mouse macrophage cell line. The screen identified 364 candidate immunoregulatory genes. To illustrate the utility of the candidate list, we confirmed the impact of 35 Mtb mutant strains on expression of endogenous immune response genes in primary macrophages. Detailed analysis focused on a strain of Mtb in which a transposon disrupts Rv0431, a gene encoding a conserved protein of unknown function. This mutant elicited much more macrophage TNFα, IL-12p40 and IL-6 in vitro than wild type Mtb, and was attenuated in the mouse. The mutant list provides a platform for exploring the immunobiology of tuberculosis, for example, by combining immunoregulatory mutations in a candidate vaccine strain.http://europepmc.org/articles/PMC3000826?pdf=render |
| spellingShingle | Aimee M Beaulieu Poonam Rath Marianne Imhof Mark E Siddall Julia Roberts Dirk Schnappinger Carl F Nathan Genome-wide screen for Mycobacterium tuberculosis genes that regulate host immunity. PLoS ONE |
| title | Genome-wide screen for Mycobacterium tuberculosis genes that regulate host immunity. |
| title_full | Genome-wide screen for Mycobacterium tuberculosis genes that regulate host immunity. |
| title_fullStr | Genome-wide screen for Mycobacterium tuberculosis genes that regulate host immunity. |
| title_full_unstemmed | Genome-wide screen for Mycobacterium tuberculosis genes that regulate host immunity. |
| title_short | Genome-wide screen for Mycobacterium tuberculosis genes that regulate host immunity. |
| title_sort | genome wide screen for mycobacterium tuberculosis genes that regulate host immunity |
| url | http://europepmc.org/articles/PMC3000826?pdf=render |
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