Project Description:

Having pneumonia in mid- to late-life accelerates or exacerbates other health conditions such as cognitive decline, cardiovascular issues, and frailty. Because we don’t know why this occurs, the only way to prevent it is to reduce the risk of infection by vaccination. We don’t have vaccines against all the pathogens that cause pneumonia and even if we did, not all older adults respond perfectly to vaccines. Our vision is to understand how pneumonia causes long-term health issues and test interventions in our pre-clinical models to develop new treatments.

Our ongoing investigations include;

1. Understanding how age-related changes in the immune response increase the risk of pneumonia.
2. Using large population-based studies to understand how pneumonia and chronic inflammation impact cognition (led by collaborator Dr. Chris Verschoor)
3. Understanding how chronic age-associated inflammation impact microglia (brain macrophage) function
4. Uncovering mechanisms by which pneumonia impacts cognition and accelerates frailty.
5. Testing new drugs to prevent post-pneumonia cognitive decline.

Team Members:
Technical lead: Braeden Cowborough
Graduate students: Sofya Ermolina (PhD)
Undergraduate students:  Molly Health, Amanda Densil

Current Funding: CIHR Brain Aging Team Grant (co-PI, Dr Chris Verschoor, co-investigators Drs A. Costa, A. Jones, M. Chong, K. Choe, C. Quin, J. Kwong, M. Tremblay)

Publications:

1.	Acute organ injury and long-term sequelae of severe pneumococcal infections. Kruckow KL, Zhao K, Bowdish DME, Orihuela CJ. Pneumonia (Nathan). 2023 Mar 5;15(1):5. doi: 10.1186/s41479-023-00110-y. PMID: 36870980 Free PMC article. Review.
2.	Autoantibody-mediated Macrophage Dysfunction in Patients with Severe Asthma with Airway Infections. Son K, Miyasaki K, Salter B, Loukov D, Chon J, Zhao N, Radford K, Huang C, LaVigne N, Dvorkin-Gheva A, Lacy P, Ho T, Bowdish DME, Nair P, Mukherjee M. Am J Respir Crit Care Med. 2023 Feb 15;207(4):427-437. doi: 10.1164/rccm.202206-1183OC. PMID: 36287613
3.	Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction. Thevaranjan N, Puchta A, Schulz C, Naidoo A, Szamosi JC, Verschoor CP, Loukov D, Schenck LP, Jury J, Foley KP, Schertzer JD, Larché MJ, Davidson DJ, Verdú EF, Surette MG, Bowdish DME. Cell Host Microbe. 2017 Apr 12;21(4):455-466.e4. doi: 10.1016/j.chom.2017.03.002. PMID: 28407483 Free PMC article.
4.	TNF Drives Monocyte Dysfunction with Age and Results in Impaired Anti-pneumococcal Immunity. Puchta A, Naidoo A, Verschoor CP, Loukov D, Thevaranjan N, Mandur TS, Nguyen PS, Jordana M, Loeb M, Xing Z, Kobzik L, Larché MJ, Bowdish DM. PLoS Pathog. 2016 Jan 14;12(1):e1005368. doi: 10.1371/journal.ppat.1005368. eCollection 2016 Jan. PMID: 26766566 Free PMC article.
5.	Anti-pneumococcal deficits of monocyte-derived macrophages from the advanced-age, frail elderly and related impairments in PI3K-AKT signaling. Verschoor CP, Johnstone J, Loeb M, Bramson JL, Bowdish DM. Hum Immunol. 2014 Dec;75(12):1192-6. doi: 10.1016/j.humimm.2014.10.004. Epub 2014 Oct 13. PMID: 25446401
6.	Characterization of inflammatory responses during intranasal colonization with Streptococcus pneumoniae. Puchta A, Verschoor CP, Thurn T, Bowdish DM. J Vis Exp. 2014 Jan 17;(83):e50490. doi: 10.3791/50490. PMID: 24472828 Free PMC article.