Clade-Specific Virulence Patterns of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Complex Strains in Human Primary Macrophages and Aerogenically Infected Mice

ABSTRACT In infection experiments with genetically distinct Mycobacterium tuberculosis complex (MTBC) strains, we identified clade-specific virulence patterns in human primary macrophages and in mice infected by the aerosol route, both reflecting relevant model systems. Exclusively human-adapted M....

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Autores principales:	Norbert Reiling, Susanne Homolka, Kerstin Walter, Julius Brandenburg, Lisa Niwinski, Martin Ernst, Christian Herzmann, Christoph Lange, Roland Diel, Stefan Ehlers, Stefan Niemann
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ce4627a1bc1045cab296ce10d29533f1
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spelling	oai:doaj.org-article:ce4627a1bc1045cab296ce10d29533f12021-11-15T15:43:09ZClade-Specific Virulence Patterns of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Complex Strains in Human Primary Macrophages and Aerogenically Infected Mice10.1128/mBio.00250-132150-7511https://doaj.org/article/ce4627a1bc1045cab296ce10d29533f12013-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00250-13https://doaj.org/toc/2150-7511ABSTRACT In infection experiments with genetically distinct Mycobacterium tuberculosis complex (MTBC) strains, we identified clade-specific virulence patterns in human primary macrophages and in mice infected by the aerosol route, both reflecting relevant model systems. Exclusively human-adapted M. tuberculosis lineages, also termed clade I, comprising “modern” lineages, such as Beijing and Euro-American Haarlem strains, showed a significantly enhanced capability to grow compared to that of clade II strains, which include “ancient” lineages, such as, e.g., East African Indian or M. africanum strains. However, a simple correlation of inflammatory response profiles with strain virulence was not apparent. Overall, our data reveal three different pathogenic profiles: (i) strains of the Beijing lineage are characterized by low uptake, low cytokine induction, and a high replicative potential, (ii) strains of the Haarlem lineage by high uptake, high cytokine induction, and high growth rates, and (iii) EAI strains by low uptake, low cytokine induction, and a low replicative potential. Our findings have significant implications for our understanding of host-pathogen interaction and factors that modulate the outcomes of infections. Future studies addressing the underlying mechanisms and clinical implications need to take into account the diversity of both the pathogen and the host. IMPORTANCE Clinical strains of the Mycobacterium tuberculosis complex (MTBC) are genetically more diverse than previously anticipated. Our analysis of mycobacterial growth characteristics in primary human macrophages and aerogenically infected mice shows that the MTBC genetic differences translate into pathogenic differences in the interaction with the host. Our study reveals for the first time that “TB is not TB,” if put in plain terms. We are convinced that it is very unlikely that a single molecular mechanism may explain the observed effects. Our study refutes the hypothesis that there is a simple correlation between cytokine induction as a single functional parameter of host interaction and mycobacterial virulence. Instead, careful consideration of strain- and lineage-specific characteristics must guide our attempts to decipher what determines the pathological potential and thus the outcomes of infection with MTBC, one of the most important human pathogens.Norbert ReilingSusanne HomolkaKerstin WalterJulius BrandenburgLisa NiwinskiMartin ErnstChristian HerzmannChristoph LangeRoland DielStefan EhlersStefan NiemannAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 4 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Norbert Reiling Susanne Homolka Kerstin Walter Julius Brandenburg Lisa Niwinski Martin Ernst Christian Herzmann Christoph Lange Roland Diel Stefan Ehlers Stefan Niemann Clade-Specific Virulence Patterns of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Complex Strains in Human Primary Macrophages and Aerogenically Infected Mice
description	ABSTRACT In infection experiments with genetically distinct Mycobacterium tuberculosis complex (MTBC) strains, we identified clade-specific virulence patterns in human primary macrophages and in mice infected by the aerosol route, both reflecting relevant model systems. Exclusively human-adapted M. tuberculosis lineages, also termed clade I, comprising “modern” lineages, such as Beijing and Euro-American Haarlem strains, showed a significantly enhanced capability to grow compared to that of clade II strains, which include “ancient” lineages, such as, e.g., East African Indian or M. africanum strains. However, a simple correlation of inflammatory response profiles with strain virulence was not apparent. Overall, our data reveal three different pathogenic profiles: (i) strains of the Beijing lineage are characterized by low uptake, low cytokine induction, and a high replicative potential, (ii) strains of the Haarlem lineage by high uptake, high cytokine induction, and high growth rates, and (iii) EAI strains by low uptake, low cytokine induction, and a low replicative potential. Our findings have significant implications for our understanding of host-pathogen interaction and factors that modulate the outcomes of infections. Future studies addressing the underlying mechanisms and clinical implications need to take into account the diversity of both the pathogen and the host. IMPORTANCE Clinical strains of the Mycobacterium tuberculosis complex (MTBC) are genetically more diverse than previously anticipated. Our analysis of mycobacterial growth characteristics in primary human macrophages and aerogenically infected mice shows that the MTBC genetic differences translate into pathogenic differences in the interaction with the host. Our study reveals for the first time that “TB is not TB,” if put in plain terms. We are convinced that it is very unlikely that a single molecular mechanism may explain the observed effects. Our study refutes the hypothesis that there is a simple correlation between cytokine induction as a single functional parameter of host interaction and mycobacterial virulence. Instead, careful consideration of strain- and lineage-specific characteristics must guide our attempts to decipher what determines the pathological potential and thus the outcomes of infection with MTBC, one of the most important human pathogens.
format	article
author	Norbert Reiling Susanne Homolka Kerstin Walter Julius Brandenburg Lisa Niwinski Martin Ernst Christian Herzmann Christoph Lange Roland Diel Stefan Ehlers Stefan Niemann
author_facet	Norbert Reiling Susanne Homolka Kerstin Walter Julius Brandenburg Lisa Niwinski Martin Ernst Christian Herzmann Christoph Lange Roland Diel Stefan Ehlers Stefan Niemann
author_sort	Norbert Reiling
title	Clade-Specific Virulence Patterns of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Complex Strains in Human Primary Macrophages and Aerogenically Infected Mice
title_short	Clade-Specific Virulence Patterns of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Complex Strains in Human Primary Macrophages and Aerogenically Infected Mice
title_full	Clade-Specific Virulence Patterns of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Complex Strains in Human Primary Macrophages and Aerogenically Infected Mice
title_fullStr	Clade-Specific Virulence Patterns of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Complex Strains in Human Primary Macrophages and Aerogenically Infected Mice
title_full_unstemmed	Clade-Specific Virulence Patterns of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Complex Strains in Human Primary Macrophages and Aerogenically Infected Mice
title_sort	clade-specific virulence patterns of <named-content content-type="genus-species">mycobacterium tuberculosis</named-content> complex strains in human primary macrophages and aerogenically infected mice
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/ce4627a1bc1045cab296ce10d29533f1
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Clade-Specific Virulence Patterns of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Complex Strains in Human Primary Macrophages and Aerogenically Infected Mice

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