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 | |
| State | Published - Jul 2 2019 |
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Keywords
- aging
- alveolar lining fluid
- mycobacteria
- oxidation
- surfactant
- tuberculosis
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases
Cite this
The Lung Mucosa Environment in the Elderly Increases Host Susceptibility to Mycobacterium tuberculosis Infection. / Moliva, Juan I.; Duncan, Michael A.; Olmo-Fontánez, Angélica; Akhter, Anwari; Arnett, Eusondia; Scordo, Julia M.; Ault, Russell; Sasindran, Smitha J.; Azad, Abul K.; Montoya, Maria J.; Reinhold-Larsson, Nicole; Rajaram, Murugesan V.S.; Merrit, Robert E.; Lafuse, William P.; Zhang, Liwen; Wang, Shu Hua; Beamer, Gillian; Wang, Yufeng; Proud, Kevin; Maselli, Diego Jose; Peters, Jay I; Weintraub, Susan E; Turner, Joanne; Schlesinger, Larry S.; Torrelles, Jordi B.
In: Journal of Infectious Diseases, Vol. 220, No. 3, jiz138, 02.07.2019, p. 514-523.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Lung Mucosa Environment in the Elderly Increases Host Susceptibility to Mycobacterium tuberculosis Infection
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 I
AU - Weintraub, Susan E
AU - Turner, Joanne
AU - Schlesinger, Larry S.
AU - Torrelles, Jordi B.
PY - 2019/7/2
Y1 - 2019/7/2
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
UR - http://www.scopus.com/inward/record.url?scp=85070069461&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070069461&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiz138
DO - 10.1093/infdis/jiz138
M3 - Article
VL - 220
SP - 514
EP - 523
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 3
M1 - jiz138
ER -