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

Abstract

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.

The pathogenesis of cardiac microlesion formation during severe bacteremic infection

“…More recently, the human commensal gram-positive bacterium Enterococcus faecalis was also shown to promote cardiac microlesion formation in mice, while suppressing the host cardiomyocyte inflammatory response in vitro [ 3 ]. Similar observations of microlesion formation were made with the gram-negative bacterium Franscisella tularensis subspecies novicida [ 4 ] and gram-positive bacterium non-tuberculosis Mycobacterium avium [ 5 ]. Therefore, cardiac microlesion formation is becoming increasingly appreciated as a possible risk factor for adverse cardiac complications during severe bacterial infection [ 6 ].…”

“…Ft.n microlesions were associated with altered electrophysiology, cardiomyocyte cell death, increased production of inflammatory mediators in the blood, and myocardial inflammation [4]. Likewise, during severe infection of mice with non-tuberculosis M. avium, cardiac microlesions were observed to be associated with increased inflammatory mediators in the blood, altered electrophysiology, cardiac hypertrophy, premature atrial contraction, and cardiac dysrhythmia in old mice [5]. Although inflammatory mediators could be detected within the serum or hearts of mice infected with Ft.n and M. avium, the cardiac microlesion pathology observed is similar to those caused by S. pneumoniae and E. faecalis.…”

Role of Cardiac Macrophages on Cardiac Inflammation, Fibrosis and Tissue Repair

“…The most common causes of myocarditis are infections of various pathogens including parasite Trypanosoma cruzi in South America, or viruses, such as enterovirus, parvovirus B19, adenovirus and hepatitis C virus, which are the major causes in North America [ 52 , 53 , 54 ]. Recently, we and others have shown that bacterial infection also induces myocardial inflammation and cardiac dysfunction [ 55 , 56 , 57 , 58 , 59 , 60 ]. In addition, non-infectious agents, such as allergic reactions to drugs and chemicals, can induce cardiomyocyte apoptosis and the release of DAMPs, which activate the innate immune response leading to sterile inflammation and myocarditis [ 53 ].…”

“…Due to increased myocardial cell apoptosis and clearance of dead cells, cardiac fibrosis is induced and causes severe damage to cardiac electrical conduction [ 60 ]. Furthermore, we demonstrated that the M. avium infection in aged mice enhances the recruitment of CD45 + leukocytes into the heart and increased expression of inflammatory cytokines, which results in the induction of cardiac fibrosis and cardiac hypertrophy [ 59 ]. In addition, many bacterial, fungal and viral infections cause inflammation in the endocardium of the heart [ 111 ].…”

Aging heart and infection

“…We examined how mycobacterial infection and inflammaging catalyze the decline in cardiovascular function in the elderly [6]. Young (3 months) and old (18 month) female C57BL/6 mice were infected with a sub-lethal dose of , Mycobacterium avium (M. avium), an NTM.…”