The Lung Mucosa Environment in the Elderly Increases Host Susceptibility to Mycobacterium tuberculosis Infection

Juan I. Moliva; Michael A. Duncan; Angélica Olmo-Fontánez; Anwari Akhter; Eusondia Arnett; Julia M. Scordo; Russell Ault; Smitha J. Sasindran; Abul K. Azad; Maria J. Montoya; Nicole Reinhold-Larsson; Murugesan V.S. Rajaram; Robert E. Merrit; William P. Lafuse; Liwen Zhang; Shu Hua Wang; Gillian Beamer; Yufeng Wang; Kevin Proud; Diego Jose Maselli; Jay Peters; Susan T. Weintraub; Joanne Turner; Larry S. Schlesinger; Jordi B. Torrelles

doi:10.1093/infdis/jiz138

The Lung Mucosa Environment in the Elderly Increases Host Susceptibility to Mycobacterium tuberculosis Infection

Juan I. Moliva, Michael A. Duncan, Angélica Olmo-Fontánez, Anwari Akhter, Eusondia Arnett, Julia M. Scordo, Russell Ault, Smitha J. Sasindran, Abul K. Azad, Maria J. Montoya, Nicole Reinhold-Larsson, Murugesan V.S. Rajaram, Robert E. Merrit, William P. Lafuse, Liwen Zhang, Shu Hua Wang, Gillian Beamer, Yufeng Wang, Kevin Proud, Diego Jose MaselliJay Peters, Susan T. Weintraub, Joanne Turner, Larry S. Schlesinger, Jordi B. Torrelles

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

As we age, there is an increased risk for the development of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection. Few studies consider that age-associated changes in the alveolar lining fluid (ALF) may increase susceptibility by altering soluble mediators of innate immunity. We assessed the impact of adult or elderly human ALF during Mtb infection in vitro and in vivo. We identified amplification of pro-oxidative and proinflammatory pathways in elderly ALF and decreased binding capability of surfactant-associated surfactant protein A (SP-A) and surfactant protein D (SP-D) to Mtb. Human macrophages infected with elderly ALF-exposed Mtb had reduced control and fewer phagosome-lysosome fusion events, which was reversed when elderly ALF was replenished with functional SP-A/SP-D. In vivo, exposure to elderly ALF exacerbated Mtb infection in young mice. Our studies demonstrate how the pulmonary environment changes as we age and suggest that Mtb may benefit from declining host defenses in the lung mucosa of the elderly.

Original language	English (US)
Article number	jiz138
Pages (from-to)	514-523
Number of pages	10
Journal	Journal of Infectious Diseases
Volume	220
Issue number	3
DOIs	https://doi.org/10.1093/infdis/jiz138
State	Published - Jul 2 2019
Externally published	Yes

Keywords

aging
alveolar lining fluid
mycobacteria
oxidation
surfactant
tuberculosis

ASJC Scopus subject areas

General Medicine

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10.1093/infdis/jiz138

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Moliva, J. I., Duncan, M. A., Olmo-Fontánez, A., Akhter, A., Arnett, E., Scordo, J. M., Ault, R., Sasindran, S. J., Azad, A. K., Montoya, M. J., Reinhold-Larsson, N., Rajaram, M. V. S., Merrit, R. E., Lafuse, W. P., Zhang, L., Wang, S. H., Beamer, G., Wang, Y., Proud, K., ... Torrelles, J. B. (2019). The Lung Mucosa Environment in the Elderly Increases Host Susceptibility to Mycobacterium tuberculosis Infection. Journal of Infectious Diseases, 220(3), 514-523. Article jiz138. https://doi.org/10.1093/infdis/jiz138

Moliva, JI, Duncan, MA, Olmo-Fontánez, A, Akhter, A, Arnett, E, Scordo, JM, Ault, R, Sasindran, SJ, Azad, AK, Montoya, MJ, Reinhold-Larsson, N, Rajaram, MVS, Merrit, RE, Lafuse, WP, Zhang, L, Wang, SH, Beamer, G, Wang, Y, Proud, K , Maselli, DJ , Peters, J , Weintraub, ST, Turner, J, Schlesinger, LS & Torrelles, JB 2019, 'The Lung Mucosa Environment in the Elderly Increases Host Susceptibility to Mycobacterium tuberculosis Infection', Journal of Infectious Diseases, vol. 220, no. 3, jiz138, pp. 514-523. https://doi.org/10.1093/infdis/jiz138

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title = "The Lung Mucosa Environment in the Elderly Increases Host Susceptibility to Mycobacterium tuberculosis Infection",

abstract = "As we age, there is an increased risk for the development of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection. Few studies consider that age-associated changes in the alveolar lining fluid (ALF) may increase susceptibility by altering soluble mediators of innate immunity. We assessed the impact of adult or elderly human ALF during Mtb infection in vitro and in vivo. We identified amplification of pro-oxidative and proinflammatory pathways in elderly ALF and decreased binding capability of surfactant-associated surfactant protein A (SP-A) and surfactant protein D (SP-D) to Mtb. Human macrophages infected with elderly ALF-exposed Mtb had reduced control and fewer phagosome-lysosome fusion events, which was reversed when elderly ALF was replenished with functional SP-A/SP-D. In vivo, exposure to elderly ALF exacerbated Mtb infection in young mice. Our studies demonstrate how the pulmonary environment changes as we age and suggest that Mtb may benefit from declining host defenses in the lung mucosa of the elderly.",

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AU - Moliva, Juan I.

AU - Duncan, Michael A.

AU - Olmo-Fontánez, Angélica

AU - Akhter, Anwari

AU - Arnett, Eusondia

AU - Scordo, Julia M.

AU - Ault, Russell

AU - Sasindran, Smitha J.

AU - Azad, Abul K.

AU - Montoya, Maria J.

AU - Reinhold-Larsson, Nicole

AU - Rajaram, Murugesan V.S.

AU - Merrit, Robert E.

AU - Lafuse, William P.

AU - Zhang, Liwen

AU - Wang, Shu Hua

AU - Beamer, Gillian

AU - Wang, Yufeng

AU - Proud, Kevin

AU - Maselli, Diego Jose

AU - Peters, Jay

AU - Weintraub, Susan T.

AU - Turner, Joanne

AU - Schlesinger, Larry S.

AU - Torrelles, Jordi B.

PY - 2019/7/2

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N2 - As we age, there is an increased risk for the development of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection. Few studies consider that age-associated changes in the alveolar lining fluid (ALF) may increase susceptibility by altering soluble mediators of innate immunity. We assessed the impact of adult or elderly human ALF during Mtb infection in vitro and in vivo. We identified amplification of pro-oxidative and proinflammatory pathways in elderly ALF and decreased binding capability of surfactant-associated surfactant protein A (SP-A) and surfactant protein D (SP-D) to Mtb. Human macrophages infected with elderly ALF-exposed Mtb had reduced control and fewer phagosome-lysosome fusion events, which was reversed when elderly ALF was replenished with functional SP-A/SP-D. In vivo, exposure to elderly ALF exacerbated Mtb infection in young mice. Our studies demonstrate how the pulmonary environment changes as we age and suggest that Mtb may benefit from declining host defenses in the lung mucosa of the elderly.

AB - As we age, there is an increased risk for the development of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection. Few studies consider that age-associated changes in the alveolar lining fluid (ALF) may increase susceptibility by altering soluble mediators of innate immunity. We assessed the impact of adult or elderly human ALF during Mtb infection in vitro and in vivo. We identified amplification of pro-oxidative and proinflammatory pathways in elderly ALF and decreased binding capability of surfactant-associated surfactant protein A (SP-A) and surfactant protein D (SP-D) to Mtb. Human macrophages infected with elderly ALF-exposed Mtb had reduced control and fewer phagosome-lysosome fusion events, which was reversed when elderly ALF was replenished with functional SP-A/SP-D. In vivo, exposure to elderly ALF exacerbated Mtb infection in young mice. Our studies demonstrate how the pulmonary environment changes as we age and suggest that Mtb may benefit from declining host defenses in the lung mucosa of the elderly.

KW - aging

KW - alveolar lining fluid

KW - mycobacteria

KW - oxidation

KW - surfactant

KW - tuberculosis

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The Lung Mucosa Environment in the Elderly Increases Host Susceptibility to Mycobacterium tuberculosis Infection

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Keywords

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