Mycobacterium abscessus induces immune suppression in cystic fibrosis macrophages
6 affiliations
- 1Department of Microbial Infection & Immunity, The Ohio State University, Columbus, OH, United States
- 2Center for Microbe and Immunity Research, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, United States
- 3Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, United States
- 4Division of Pulmonary Medicine, Nationwide Children’s Hospital, Columbus, OH, United States
- 5Center for Perinatal Research, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, United States
- 6Infectious Disease Institute, The Ohio State University, Columbus, OH, United States
Abstract
IntroductionPeople with cystic fibrosis (pwCF) are highly susceptible to chronic lung infections with Mycobacterium abscessus (MAB), a nontuberculous mycobacterium (NTM) that is intrinsically resistant to antibiotics. While macrophage dysfunction is recognized in CF, responses to MAB in primary human macrophages remain poorly defined.MethodsWe investigated the innate immune response to MAB using peripheral blood monocytes and monocyte-derived macrophages from pwCF and healthy donors. Macrophages were infected with opsonized smooth (MAS) or rough (MAR) isolates of MAB morphotypes at low multiplicity of infection. After removal of extracellular bacteria, intracellular burden, oxidative burst, NOX2 activation, and cytokine production were assessed at 2- and 24-hours post-infection.ResultsMAB uptake was comparable across all groups and non-CF macrophages showed no difference in intracellular MAR or MAS at 24h. In contrast, CF macrophages harbored significantly more intracellular MAR at 24 hours, a phenotype recapitulated by CFTR knockdown in non-CF macrophages. MAB-infected CF macrophages demonstrated a significantly reduced oxidative burst and diminished NOX2 p47phox phosphorylation. Non-CF macrophages treated with CFTR inhibitor mimicked the reduced oxidative burst. CF macrophages also exhibited an altered cytokine response with significantly elevated IL-8 but decreased IL-1β relative to healthy macrophages. Notably, MAR-infected CF macrophages secreted significantly less TNF-α compared with non-CF macrophages and exhibited markedly reduced apoptosis compared with MAR-infected non-CF and MAS-infected CF macrophages.DiscussionThese findings demonstrate that CF macrophages are intrinsically impaired in their ability to control the virulent rough MAB morphotype, highlighting a potential mechanism for persistent NTM infection in pwCF and underscoring the need for host-directed therapies.
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BibTeX
@article{hill2026mycobacterium,
title = {{Mycobacterium abscessus induces immune suppression in cystic fibrosis macrophages}},
author = {Preston J. Hill and Christopher J. Miller and Raul Rascon and Gillian Clary and Ayantu W. Idosa and Mikhail A. Gavrilin and Karen S. McCoy and Amal O. Amer and Santiago Partida-Sanchez and Benjamin T. Kopp and Benjamin T. Kopp and Luanne Hall-Stoodley and Luanne Hall-Stoodley},
journal = {Frontiers in Cellular and Infection Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1903803},
url = {https://doi.org/10.3389/fcimb.2026.1903803},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mycobacterium abscessus induces immune suppression in cystic fibrosis macrophages
AU - Preston J. Hill
AU - Christopher J. Miller
AU - Raul Rascon
AU - Gillian Clary
AU - Ayantu W. Idosa
AU - Mikhail A. Gavrilin
AU - Karen S. McCoy
AU - Amal O. Amer
AU - Santiago Partida-Sanchez
AU - Benjamin T. Kopp
AU - Benjamin T. Kopp
AU - Luanne Hall-Stoodley
AU - Luanne Hall-Stoodley
PY - 2026
DA - 2026/10/27
JO - Frontiers in Cellular and Infection Microbiology
DO - 10.3389/fcimb.2026.1903803
UR - https://doi.org/10.3389/fcimb.2026.1903803
AB - IntroductionPeople with cystic fibrosis (pwCF) are highly susceptible to chronic lung infections with Mycobacterium abscessus (MAB), a nontuberculous mycobacterium (NTM) that is intrinsically resistant to antibiotics. While macrophage dysfunction is recognized in CF, responses to MAB in primary human macrophages remain poorly defined.MethodsWe investigated the innate immune response to MAB using peripheral blood monocytes and monocyte-derived macrophages from pwCF and healthy donors. Macrophages were infected with opsonized smooth (MAS) or rough (MAR) isolates of MAB morphotypes at low multiplicity of infection. After removal of extracellular bacteria, intracellular burden, oxidative burst, NOX2 activation, and cytokine production were assessed at 2- and 24-hours post-infection.ResultsMAB uptake was comparable across all groups and non-CF macrophages showed no difference in intracellular MAR or MAS at 24h. In contrast, CF macrophages harbored significantly more intracellular MAR at 24 hours, a phenotype recapitulated by CFTR knockdown in non-CF macrophages. MAB-infected CF macrophages demonstrated a significantly reduced oxidative burst and diminished NOX2 p47phox phosphorylation. Non-CF macrophages treated with CFTR inhibitor mimicked the reduced oxidative burst. CF macrophages also exhibited an altered cytokine response with significantly elevated IL-8 but decreased IL-1β relative to healthy macrophages. Notably, MAR-infected CF macrophages secreted significantly less TNF-α compared with non-CF macrophages and exhibited markedly reduced apoptosis compared with MAR-infected non-CF and MAS-infected CF macrophages.DiscussionThese findings demonstrate that CF macrophages are intrinsically impaired in their ability to control the virulent rough MAB morphotype, highlighting a potential mechanism for persistent NTM infection in pwCF and underscoring the need for host-directed therapies.
SN - 2235-2988
ER -