Immunological and Microbial Shifts in the Aging Rhesus Macaque Lung During Nontuberculous Mycobacterial Infection

Overview

Journal mBio

Publisher American Society for Microbiology

Specialty Microbiology

Date 2024 May 21

PMID 38771046

Authors

Isaac R Cinco

Ethan G Napier

Nicholas S Rhoades

Michael H Davies

Derek B Allison

Steven G Kohama

Luiz Bermudez

Kevin Winthrop

Cristina Fuss

Eliot R Spindel

Ilhem Messaoudi

Affiliations

Soon will be listed here.

Abstract

Importance: Nontuberculous mycobacteria (NTM) are emerging as pathogens of high consequence, as cases of NTM pulmonary disease (NTMPD) have exceeded those of . NTMPD can be debilitating, particularly in patients over 65 years of age, as it causes chronic cough and fatigue requiring prolonged treatments with antibiotics. The underlying mechanisms of this increased disease severity with age are poorly understood, hampering the development of therapeutics and vaccines. Here, we use a rhesus macaque model to investigate the impact of age on host-NTM interactions. This work shows that aging is associated with increased disease severity and bacterial persistence in aged rhesus macaques, thus providing a preclinical model to develop and test novel therapeutics and interventions.

References

Parada A, Needham D, Fuhrman J . Every base matters: assessing small subunit rRNA primers for marine microbiomes with mock communities, time series and global field samples. Environ Microbiol. 2015; 18(5):1403-14. DOI: 10.1111/1462-2920.13023. View

Chan E, Iseman M . Slender, older women appear to be more susceptible to nontuberculous mycobacterial lung disease. Gend Med. 2010; 7(1):5-18. DOI: 10.1016/j.genm.2010.01.005. View

Asquith M, Haberthur K, Brown M, Engelmann F, Murphy A, Al-Mahdi Z . Age-dependent changes in innate immune phenotype and function in rhesus macaques (Macaca mulatta). Pathobiol Aging Age Relat Dis. 2012; 2. PMC: 3417700. DOI: 10.3402/pba.v2i0.18052. View

Falkinham 3rd J . Ecology of nontuberculous mycobacteria--where do human infections come from?. Semin Respir Crit Care Med. 2013; 34(1):95-102. DOI: 10.1055/s-0033-1333568. View

Dickson R, Erb-Downward J, Freeman C, McCloskey L, Falkowski N, Huffnagle G . Bacterial Topography of the Healthy Human Lower Respiratory Tract. mBio. 2017; 8(1). PMC: 5312084. DOI: 10.1128/mBio.02287-16. View

Cowman S, van Ingen J, Griffith D, Loebinger M . Non-tuberculous mycobacterial pulmonary disease. Eur Respir J. 2019; 54(1). DOI: 10.1183/13993003.00250-2019. View

Huang H, Chung F, Lo C, Lin H, Huang Y, Yeh C . Etiology and characteristics of patients with bronchiectasis in Taiwan: a cohort study from 2002 to 2016. BMC Pulm Med. 2020; 20(1):45. PMC: 7029505. DOI: 10.1186/s12890-020-1080-7. View

OConnell M, Birkenkamp K, Kleiner D, Folio L, Holland S, Olivier K . Lung manifestations in an autopsy-based series of pulmonary or disseminated nontuberculous mycobacterial disease. Chest. 2011; 141(5):1203-1209. PMC: 3342780. DOI: 10.1378/chest.11-0425. View

Hao L, Ma J, Shi C, Lin X, Zhang Y, Jo-Lewis B . Enhanced tuberculosis clearance through the combination treatment with recombinant adenovirus-mediated granulysin delivery. Theranostics. 2020; 10(22):10046-10056. PMC: 7481412. DOI: 10.7150/thno.48052. View

10.

Saunders B, Frank A, Cooper A, Orme I . Role of gamma delta T cells in immunopathology of pulmonary Mycobacterium avium infection in mice. Infect Immun. 1998; 66(11):5508-14. PMC: 108690. DOI: 10.1128/IAI.66.11.5508-5514.1998. View

11.

Toapanta F, Ross T . Impaired immune responses in the lungs of aged mice following influenza infection. Respir Res. 2009; 10:112. PMC: 2785782. DOI: 10.1186/1465-9921-10-112. View

12.

Foell D, Wittkowski H, Vogl T, Roth J . S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules. J Leukoc Biol. 2006; 81(1):28-37. DOI: 10.1189/jlb.0306170. View

13.

Katoh K, Standley D . MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol. 2013; 30(4):772-80. PMC: 3603318. DOI: 10.1093/molbev/mst010. View

14.

Holland S . Nontuberculous mycobacteria. Am J Med Sci. 2001; 321(1):49-55. DOI: 10.1097/00000441-200101000-00008. View

15.

Callahan B, McMurdie P, Rosen M, Han A, Johnson A, Holmes S . DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016; 13(7):581-3. PMC: 4927377. DOI: 10.1038/nmeth.3869. View

16.

Lun A, Chen Y, Smyth G . It's DE-licious: A Recipe for Differential Expression Analyses of RNA-seq Experiments Using Quasi-Likelihood Methods in edgeR. Methods Mol Biol. 2016; 1418:391-416. DOI: 10.1007/978-1-4939-3578-9_19. View

17.

Liu B, Kimura Y . Local immune response to respiratory syncytial virus infection is diminished in senescence-accelerated mice. J Gen Virol. 2007; 88(Pt 9):2552-2558. DOI: 10.1099/vir.0.83089-0. View

18.

Gonzalez-Navajas J, Lee J, David M, Raz E . Immunomodulatory functions of type I interferons. Nat Rev Immunol. 2012; 12(2):125-35. PMC: 3727154. DOI: 10.1038/nri3133. View

19.

Chakraborty P, Bajeli S, Kaushal D, Radotra B, Kumar A . Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis. Nat Commun. 2021; 12(1):1606. PMC: 7952908. DOI: 10.1038/s41467-021-21748-6. View

20.

Silveira-Mattos P, Narendran G, Akrami K, Fukutani K, Anbalagan S, Nayak K . Author Correction: Differential expression of CXCR3 and CCR6 on CD4 T-lymphocytes with distinct memory phenotypes characterizes tuberculosis-associated immune reconstitution inflammatory syndrome. Sci Rep. 2019; 9(1):8036. PMC: 6533265. DOI: 10.1038/s41598-019-44429-3. View