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

Sheetal Verma, Kamlesh Bhatt, Arianne Lovey, Rodrigo Ribeiro-Rodrigues, Joan Durbin, Edward C. Jones-López, Moises Palaci, Solange A. Vinhas, David Alland, Reynaldo Dietze, Jerrold J. Ellner, Padmini Salgame

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9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere1007613
JournalPLoS Pathogens
Volume15
Issue number3
DOIs
Publication statusPublished - Mar 2019

UN Sustainable Development Goals (SDGs)

  • SDG 3 - Good Health and Well-Being

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