@article{87c1f4661ee04e6b9d00c579d0593cd8,
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.",
keywords = "aging, alveolar lining fluid, mycobacteria, oxidation, surfactant, tuberculosis",
author = "Moliva, {Juan I.} and Duncan, {Michael A.} and Ang{\'e}lica Olmo-Font{\'a}nez and Anwari Akhter and Eusondia Arnett and Scordo, {Julia M.} and Russell Ault and Sasindran, {Smitha J.} and Azad, {Abul K.} and Montoya, {Maria J.} and Nicole Reinhold-Larsson and Rajaram, {Murugesan V.S.} and Merrit, {Robert E.} and Lafuse, {William P.} and Liwen Zhang and Wang, {Shu Hua} and Gillian Beamer and Yufeng Wang and Kevin Proud and Maselli, {Diego Jose} and Jay Peters and Weintraub, {Susan T.} and Joanne Turner and Schlesinger, {Larry S.} and Torrelles, {Jordi B.}",
note = "Funding Information: Financial support. This work was supported by the National Institute on Aging (NIA), NIH (grant number P01 AG-051428 to J. T., J. B. T., L. S. S., W. P. L., and S. H. W.), J. B. T. was supported by Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation. J. I. M. was partially supported by the National Institute of General Medical Sciences of the NIH (grant number T32 GM068412), by a supplement by the National Institute of Allergy and Infectious Diseases of the NIH (grant number R01 AI093570-S1), and by a supplement by the NIA (grant number P01 AG-051428-S1). R. A. was supported by the OSU Dean{\textquoteright}s Distinguished University Fellowship. Publisher Copyright: {\textcopyright} The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.",
year = "2019",
month = jul,
day = "2",
doi = "10.1093/infdis/jiz138",
language = "English (US)",
volume = "220",
pages = "514--523",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "3",
}