Transmission phenotype of Mycobacterium tuberculosis strains is mechanistically linked to induction of distinct pulmonary pathology.


Journal

PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921

Informations de publication

Date de publication:
03 2019
Historique:
received: 18 06 2018
accepted: 02 02 2019
revised: 18 03 2019
pubmed: 7 3 2019
medline: 12 4 2019
entrez: 7 3 2019
Statut: epublish

Résumé

In a study of household contacts (HHC), households were categorized into High (HT) and Low (LT) transmission groups based on the proportion of HHC with a positive tuberculin skin test. The Mycobacterium tuberculosis (Mtb) strains from HT and LT index cases of the households were designated Mtb-HT and Mtb-LT, respectively. We found that C3HeB/FeJ mice infected with Mtb-LT strains exhibited significantly higher bacterial burden compared to Mtb-HT strains and also developed diffused inflammatory lung pathology. In stark contrast, a significant number of mice infected with Mtb-HT strains developed caseating granulomas, a lesion type with high potential to cavitate. None of the Mtb-HT infected animals developed diffused inflammatory lung pathology. A link was observed between increased in vitro replication of Mtb-LT strains and their ability to induce significantly high lipid droplet formation in macrophages. These results support that distinct early interactions of Mtb-HT and Mtb-LT strains with macrophages and subsequent differential trajectories in pathological disease may be the mechanism underlying their transmission potential.

Identifiants

pubmed: 30840702
doi: 10.1371/journal.ppat.1007613
pii: PPATHOGENS-D-18-01245
pmc: PMC6422314
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1007613

Subventions

Organisme : NIAID NIH HHS
ID : U19 AI111276
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI065663
Pays : United States

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Sheetal Verma (S)

Rutgers University-New Jersey Medical School, Department of Medicine, Centre for Emerging Pathogens, Newark, New Jersey, United States of America.

Kamlesh Bhatt (K)

Rutgers University-New Jersey Medical School, Department of Medicine, Centre for Emerging Pathogens, Newark, New Jersey, United States of America.

Arianne Lovey (A)

Rutgers University-New Jersey Medical School, Department of Medicine, Centre for Emerging Pathogens, Newark, New Jersey, United States of America.

Rodrigo Ribeiro-Rodrigues (R)

Cellular and Molecular Immunology Laboratory, Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brazil.

Joan Durbin (J)

Rutgers University-New Jersey Medical School, Department of Pathology, Newark, New Jersey, United States of America.

Edward C Jones-López (EC)

Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America.

Moises Palaci (M)

Mycobacteriology Laboratory, Núcleo de Doenças de Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brazil.

Solange A Vinhas (SA)

Mycobacteriology Laboratory, Núcleo de Doenças de Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brazil.

David Alland (D)

Rutgers University-New Jersey Medical School, Department of Medicine, Centre for Emerging Pathogens, Newark, New Jersey, United States of America.

Reynaldo Dietze (R)

Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brazil.
Global Health & Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal.

Jerrold J Ellner (JJ)

Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America.

Padmini Salgame (P)

Rutgers University-New Jersey Medical School, Department of Medicine, Centre for Emerging Pathogens, Newark, New Jersey, United States of America.

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Classifications MeSH