# Biology of the human lung mucosa in aging and tuberculosis

> **NIH NIH P01** · TEXAS BIOMEDICAL RESEARCH INSTITUTE · 2020 · $338,685

## Abstract

Age-associated immune defects are considered a primary risk factor for TB, but other factors such as the 
heightened systemic inflammatory state (inflammaging) observed in elderly individuals have not been 
previously considered. During infection, airborne Mycobacterium tuberculosis (M.tb) is deposited in the lung 
where it is exposed to different local environments over time. First, M.tb encounters the alveolar space, where 
it will be in direct contact with Alveolar Lining Fluid (ALF) components, notably surfactant and complement, for 
an undetermined period. We hypothesize that ALF, containing important innate immune determinants against 
M.tb infection, is functionally deficient in old age, largely as a result of oxidative stress, which negatively 
impacts the control of M.tb infection in the lung. ALF is generated, secreted and recycled by alveolar epithelial 
cells, and is essential for maintaining lung function. Some human ALF components [surfactant proteins A (SP- 
A) and D (SP-D), homeostatic hydrolytic enzymes (hydrolases), and lipids] are critical elements of the innate 
immune system during M.tb infection, playing an important role in M.tb-phagocyte encounters. Oxidative stress 
associated with low grade chronic inflammation that occurs during aging is expected to result in changes in 
ALF component production and activity. For example, alterations in surfactant lipids are predicted to negatively 
affect SP-A and SP-D function. We know little about how oxidative stress and low grade inflammation 
associated with aging impact M.tb infection progression in the lung. This knowledge gap limits our ability to 
design new approaches for the development of diagnostics, therapeutics and vaccines that are effective in the 
lung. Here we propose to determine the function of ALF components in the elderly human lung, and their 
impact on the establishment and progression of M.tb infection using in vitro and in vivo approaches. Our 
proposal is significant and innovative in the field of aging, determining how ALF soluble components in the 
elderly lung influence M.tb infection and outcome. Our studies are closely linked to Projects 2 & 3 (innate & 
adaptive responses to M.tb infection in aging, respectively) and synergize with Project 4 (circulating molecular 
signatures of aging).

## Key facts

- **NIH application ID:** 9884702
- **Project number:** 5P01AG051428-05
- **Recipient organization:** TEXAS BIOMEDICAL RESEARCH INSTITUTE
- **Principal Investigator:** Jordi B Torrelles
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $338,685
- **Award type:** 5
- **Project period:** — → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9884702

## Citation

> US National Institutes of Health, RePORTER application 9884702, Biology of the human lung mucosa in aging and tuberculosis (5P01AG051428-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9884702. Licensed CC0.

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