Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice.
Elife
; 112022 02 03.
Article
em En
| MEDLINE
| ID: mdl-35112666
ABSTRACT
The outcome of an encounter with Mycobacterium tuberculosis (Mtb) depends on the pathogen's ability to adapt to the variable immune pressures exerted by the host. Understanding this interplay has proven difficult, largely because experimentally tractable animal models do not recapitulate the heterogeneity of tuberculosis disease. We leveraged the genetically diverse Collaborative Cross (CC) mouse panel in conjunction with a library of Mtb mutants to create a resource for associating bacterial genetic requirements with host genetics and immunity. We report that CC strains vary dramatically in their susceptibility to infection and produce qualitatively distinct immune states. Global analysis of Mtb transposon mutant fitness (TnSeq) across the CC panel revealed that many virulence pathways are only required in specific host microenvironments, identifying a large fraction of the pathogen's genome that has been maintained to ensure fitness in a diverse population. Both immunological and bacterial traits can be associated with genetic variants distributed across the mouse genome, making the CC a unique population for identifying specific host-pathogen genetic interactions that influence pathogenesis.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
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Variação Genética
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Predisposição Genética para Doença
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Interações Hospedeiro-Patógeno
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Camundongos de Cruzamento Colaborativo
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Mycobacterium tuberculosis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article