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 journalArticle

3 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 languageEnglish (US)
Article numberjiz138
Pages (from-to)514-523
Number of pages10
JournalJournal of Infectious Diseases
Volume220
Issue number3
DOIs
StatePublished - Jul 2 2019

Keywords

  • aging
  • alveolar lining fluid
  • mycobacteria
  • oxidation
  • surfactant
  • tuberculosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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  • Cite this

    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. [jiz138]. https://doi.org/10.1093/infdis/jiz138