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

doi:10.1371/journal.ppat.1007613

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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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 language	English
Article number	e1007613
Journal	PLoS Pathogens
Volume	15
Issue number	3
DOIs	https://doi.org/10.1371/journal.ppat.1007613
Publication status	Published - Mar 2019

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Transmission phenotype of MycobacteriumFinal published version, 4.5 MBLicence: CC BY

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Verma, S., Bhatt, K., Lovey, A., Ribeiro-Rodrigues, R., Durbin, J., Jones-López, E. C., Palaci, M., Vinhas, S. A., Alland, D., Dietze, R., Ellner, J. J., & Salgame, P. (2019). Transmission phenotype of mycobacterium tuberculosis strains is mechanistically linked to induction of distinct pulmonary pathology. PLoS Pathogens, 15(3), Article e1007613. https://doi.org/10.1371/journal.ppat.1007613

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title = "Transmission phenotype of mycobacterium tuberculosis strains is mechanistically linked to induction of distinct pulmonary pathology",

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.",

author = "Sheetal Verma and Kamlesh Bhatt and Arianne Lovey and Rodrigo Ribeiro-Rodrigues and Joan Durbin and Jones-L{\'o}pez, {Edward C.} and Moises Palaci and Vinhas, {Solange A.} and David Alland and Reynaldo Dietze and Ellner, {Jerrold J.} and Padmini Salgame",

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Verma, S, Bhatt, K, Lovey, A, Ribeiro-Rodrigues, R, Durbin, J, Jones-López, EC, Palaci, M, Vinhas, SA, Alland, D, Dietze, R, Ellner, JJ & Salgame, P 2019, 'Transmission phenotype of mycobacterium tuberculosis strains is mechanistically linked to induction of distinct pulmonary pathology', PLoS Pathogens, vol. 15, no. 3, e1007613. https://doi.org/10.1371/journal.ppat.1007613

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AU - Verma, Sheetal

AU - Bhatt, Kamlesh

AU - Lovey, Arianne

AU - Ribeiro-Rodrigues, Rodrigo

AU - Durbin, Joan

AU - Jones-López, Edward C.

AU - Palaci, Moises

AU - Vinhas, Solange A.

AU - Alland, David

AU - Dietze, Reynaldo

AU - Ellner, Jerrold J.

AU - Salgame, Padmini

PY - 2019/3

Y1 - 2019/3

N2 - 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.

AB - 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.

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

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