Mycobacterium avium Complex Disease

Holt, Michael; Daley, Charles L.

doi:10.1007/978-3-319-93473-0_11

Cited by 2 publications

(8 citation statements)

References 150 publications

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“…Among the ∼200 different NTM species identified, pulmonary infections are caused by relatively few, mostly due to those within the SGM group known as Mycobacterium avium complex (MAC) and the RGM group known as Mycobacterium abscessus complex. Due to the paucity of truly effective antibiotic regimens for most of the clinically relevant NTM and the specter of recurrent infections, it is difficult to achieve long-lasting cure for NTM-LD (Philley et al, 2016;Holt and Daley, 2019;Philley and Griffith, 2019).…”

Section: Introductionmentioning

confidence: 99%

Differential Responses by Human Macrophages to Infection With Mycobacterium tuberculosis and Non-tuberculous Mycobacteria

et al. 2020

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Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) are formidable causes of lung diseases throughout the world. While MTB is considered to be more virulent than NTM, host factors also play a key role in disease development.To elucidate whether there are differential immune responses to various mycobacteria, THP-1 macrophages were temporally infected with MTB H37Rv or with four different NTM species. We found that cells infected with MTB had greater bacterial burden and p65 nuclear factor-kappa B (NF-κB) activation than cells infected with NTM. There was also differential expression of mRNA for interleukin-1-β (IL-1β), IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) with no distinct pattern of mRNA expression among the different mycobacteria. In contrast, at the protein level, some generalizations can be made of the cytokines and chemokines expressed. Compared to uninfected cells, the rapid-growing Mycobacterium smegmatis but not Mycobacterium abscessus induced significantly greater pro-inflammatory cytokines and IL-10, whereas both NTM individually induced greater levels of chemokines. Compared to uninfected control cells, the two slow-growing NTM and MTB differentially induced cytokine expression with Mycobacterium avium inducing more pro-inflammatory cytokines and IL-10, whereas M. avium, Mycobacterium intracellulare, and MTB inducing greater but similar levels of chemokines. MTB-infected THP-1 cells also demonstrated lower level of phagosomelysosome fusion and apoptosis than NTM-infected cells while there were differences in these macrophage functions among the NTM species. Interestingly, M. intracellulare, M. avium, and MTB have similar levels of autophagosome formation, but the levels displayed by all three were lower than for M. smegmatis and M. abscessus. This study demonstrates the differences in bacterial burden and macrophage effector functions among several clinically relevant mycobacterial species. Such disparities may, in part, account for differences in clinical outcomes among patients infected with various species of NTM as has been seen for different strains of MTB.

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Section: Introductionmentioning

confidence: 99%

Differential Responses by Human Macrophages to Infection With Mycobacterium tuberculosis and Non-tuberculous Mycobacteria

et al. 2020

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“…In this study, we successfully established pulmonary M. intracellulare infection in five of the seven healthy female marmosets. We chose female marmosets for this investigation due to the predominance of human M. avium and M. intracellulare lung disease in women [3][4][5]. The animals showed no discernable clinical signs of lung infection, such as cough, decreased activity or weight loss, suggesting that the inoculation resulted in a "sub-clinical" infection.…”

Section: Discussionmentioning

confidence: 99%

“…Mycobacterium avium complex (MAC) is the most common nontuberculous mycobacterial (NTM) respiratory pathogen in humans [1,2]. MAC comprises multiple species and subspecies including M. avium and M. intracellulare, the two most important MAC respiratory pathogens [3][4][5]. Typically, these two species are both reported as "MAC," but their environmental sources differ, and there is evidence indicating differential pathogenicity and clinical disease severity between the two species [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…Typically, these two species are both reported as "MAC," but their environmental sources differ, and there is evidence indicating differential pathogenicity and clinical disease severity between the two species [6,7]. Since MAC is ubiquitous in the environment and exposure is likely unavoidable, it is apparent that some form of host susceptibility must also be present for MAC lung disease to occur [3,4,8]. In that context, pulmonary MAC disease occurs primarily in patients with structural lung disease, especially bronchiectasis and emphysema, without demonstrable systemic immune suppression [3,4,8].…”

Section: Introductionmentioning

confidence: 99%

“…Since MAC is ubiquitous in the environment and exposure is likely unavoidable, it is apparent that some form of host susceptibility must also be present for MAC lung disease to occur [3,4,8]. In that context, pulmonary MAC disease occurs primarily in patients with structural lung disease, especially bronchiectasis and emphysema, without demonstrable systemic immune suppression [3,4,8]. Pathophysiologic questions are further complicated because MAC lung disease can evolve in two forms, either fibro-cavitary disease similarly to pulmonary tuberculosis (TB), or as a more indolent infection associated radiographically with nodules and bronchiectasis (nodular/bronchiectatic disease) [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

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A marmoset model for Mycobacterium avium complex pulmonary disease

et al. 2023

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Rationale Mycobacterium avium complex, is the most common nontuberculous mycobacterial respiratory pathogen in humans. Disease mechanisms are poorly understood due to the absence of a reliable animal model for M. avium complex pulmonary disease. Objectives The objectives of this study were to assess the susceptibility, immunologic and histopathologic responses of the common marmoset (Callithrix jacchus) to M. avium complex pulmonary infection. Methods 7 adult female marmosets underwent endobronchial inoculation with 108 colony-forming units of M. intracellulare and were monitored for 30 or 60 days. Chest radiograph was assessed at baseline (prior to infection) and at the time of sacrifice (30 days for 3 animals and 60 days for 4 animals), and bronchoalveolar lavage cytokines, histopathology and cultures of the bronchoalveolar lavage, lungs, liver and kidney were assessed at time of sacrifice. Serum cytokines were monitored at baseline and weekly for 30 days for all animals and at 60 days for those alive. Group differences in serum cytokine measurements between those that tested positive versus negative for the M. intracellulare infection were assessed using a series of linear mixed models. Measurements and main results Five of seven animals (two at 30 days and three at 60 days of infection) had positive lung cultures for M. intracellulare. Extra-pulmonary cultures were positive in three animals. All animals appeared healthy throughout the study. All five animals with positive lung cultures had radiographic changes consistent with pneumonitis. At 30 days, those with M. intracellulare lung infection showed granulomatous inflammation, while at 60 days there were fewer inflammatory changes but bronchiectasis was noted. The cytokine response in the bronchoalveolar lavage fluid was uniformly greater in the animals with positive M. intracellulare cultures than those without a productive infection, with greater levels at 30-days compared to 60-days. Similarly, serum cytokines were more elevated in the animals that had positive M. intracellulare cultures compared to those without a productive infection, peaking 14–21 days after inoculation. Conclusion Endobronchial instillation of M. intracellulare resulted in pulmonary mycobacterial infection in marmosets with a differential immune response, radiographic and histopathologic abnormalities, and an indolent course consistent with M. avium complex lung infection in humans.

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Mycobacterium avium Complex Disease

Cited by 2 publications

References 150 publications

Differential Responses by Human Macrophages to Infection With Mycobacterium tuberculosis and Non-tuberculous Mycobacteria

Differential Responses by Human Macrophages to Infection With Mycobacterium tuberculosis and Non-tuberculous Mycobacteria

A marmoset model for Mycobacterium avium complex pulmonary disease

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