Nontuberculous mycobacterium M. avium infection predisposes aged mice to cardiac abnormalities and inflammation

Biological aging dynamically alters normal immune and cardiac function, favoring the production of pro‐inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) and increased instances of cardiac distress. Cardiac failure is the primary reason for hospitalization of the elderly (65+ years). The elderly are al...

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Published in:	Aging cell Vol. 18; no. 3; pp. e12926 - n/a
Main Authors:	Headley, Colwyn A., Gerberick, Abigail, Mehta, Sumiran, Wu, Qian, Yu, Lianbo, Fadda, Paolo, Khan, Mahmood, Ganesan, Latha Prabha, Turner, Joanne, Rajaram, Murugesan V. S.
Format:	Journal Article
Language:	English
Published:	England John Wiley & Sons, Inc 01-06-2019 John Wiley and Sons Inc
Subjects:	Aging Aging - immunology Aging - pathology Analysis Animals Arrhythmia Arrhythmias, Cardiac - genetics Arrhythmias, Cardiac - metabolism Arrhythmias, Cardiac - microbiology Bacteria Bacterial infections Cardiac function Cardiomegaly - genetics Cardiomegaly - metabolism Cardiomegaly - microbiology CD45 antigen Disease Susceptibility ECG Endomyocardial Fibrosis - genetics Endomyocardial Fibrosis - metabolism Endomyocardial Fibrosis - microbiology Female Fibrosis Gene Expression Regulation - genetics Gene Expression Regulation - immunology Geriatrics Heart Hypertrophy Immune status Infections Inflammation Inflammation - microbiology Interleukin-1beta - metabolism Interleukin-6 - metabolism Leukocyte Common Antigens - immunology Leukocyte migration Mice Mice, Inbred C57BL Mycobacterium avium Mycobacterium Infections, Nontuberculous - immunology Mycobacterium Infections, Nontuberculous - pathology Nontuberculous Mycobacteria nontuberculous mycobacterium Older people Opportunist infection Original Paper Original Papers Pathogens Signal Transduction - genetics Signal Transduction - immunology Tumor necrosis factor Tumor Necrosis Factor-alpha - metabolism ECG Mycobacterium avium nontuberculous mycobacterium fibrosis aging Arrhythmia
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Summary:	Biological aging dynamically alters normal immune and cardiac function, favoring the production of pro‐inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) and increased instances of cardiac distress. Cardiac failure is the primary reason for hospitalization of the elderly (65+ years). The elderly are also increasingly susceptible to developing chronic bacterial infections due to aging associated immune abnormalities. Since bacterial infections compound the rates of cardiac failure in the elderly, and this phenomenon is not entirely understood, the interplay between the immune system and cardiovascular function in the elderly is of great interest. Using Mycobacterium avium, an opportunistic pathogen, we investigated the effect of mycobacteria on cardiac function in aged mice. Young (2–3 months) and old (18–20 months) C57BL/6 mice were intranasally infected with M. avium strain 104, and we compared the bacterial burden, immune status, cardiac electrical activity, pathology, and function of infected mice against uninfected age‐matched controls. Herein, we show that biological aging may predispose old mice infected with M. avium to mycobacterial dissemination into the heart tissue and this leads to cardiac dysfunction. M. avium infected old mice had significant dysrhythmia, cardiac hypertrophy, increased recruitment of CD45+ leukocytes, cardiac fibrosis, and increased expression of inflammatory genes in isolated heart tissue. This is the first study to report the effect of mycobacteria on cardiac function in an aged model. Our findings are critical to understanding how nontuberculous mycobacterium (NTM) and other mycobacterial infections contribute to cardiac dysfunction in the elderly population.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1474-9718 1474-9726
DOI:	10.1111/acel.12926