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

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2019 Mar 30

PMID 30923818

Citations 30

Authors

Juan I Moliva

Michael A Duncan

Angelica Olmo-Fontanez

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

Affiliations

Soon will be listed here.

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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