Cystic fibrosis CFBE41o‐ cells contain TLR1 SNP I602S and fail to respond to Mycobacterium abscessus

Kempaiah, Prakasha; Davidson, Lisa B.; Perkins, Douglas J; Byrd, Thomas F.

doi:10.1016/j.jcf.2013.01.001

Cited by 6 publications

(4 citation statements)

References 27 publications

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“…an anaerobic gram-negative bacterium belonging to the respiratory tract microbiota (43). In the case of M. abscessus , previous works demonstrated that bronchial epithelial cells generate a hyporesponsive response since M. abscessus S fail to elicit a Toll-like receptor 2 (TLR2) response and only a precise cell fraction from R morphotype exhibits TLR2 stimulating activity (44), which is necessary for the activation of the signaling cascade that triggers the secretion of the cytokines IL-6 and IL-8 (45). This lack of immune response activation observed is particularly high in the case of the S morphotype (as supported by our results) since the presence of GPL in its cell wall masks other molecules that would activate TLR2 signaling (46).…”

Section: Discussionmentioning

confidence: 99%

Interplay ofMycobacterium abscessusandPseudomonas aeruginosain coinfection: Biofilm Dynamics and Host Immune Response

Campo-Pérez,

Julián,

Torrents

2024

Preprint

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The incidence of infection by nontuberculous mycobacteria, mainly Mycobacterium abscessus, in patients with cystic fibrosis and other chronic pulmonary illnesses is increasing, translating into an acceleration in the decline of lung function. In most cases, M. abscessus coinfects with Pseudomonas aeruginosa, the most common pathogen in these chronic diseases. However, it is unknown how these two bacterial species interact when coinfecting. This study aims to explore the behavior of both species in three relevant pathogenic settings: dual-species biofilm development using a recently developed method to monitor individual species in dual-species biofilms; coinfection in bronchial epithelial cells using in vitro assays; and in vivo coinfection using the Galleria mellonella model. The results demonstrate the capability of both species to form stable mixed biofilms and to reciprocally inhibit single-biofilm progression. Coinfections in bronchial epithelial cells were correlated with significantly decreased cell viability, while in G. mellonella, coinfections induced lower survival rates than individual infections. Outstandingly, the analysis of the immune response triggered by each bacterium in bronchial epithelial cell assays and G. mellonella larvae revealed that P. aeruginosa induces the overexpression of proinflammatory and melanization cascade responses, respectively. In contrast, M. abscessus and P. aeruginosa coinfection significantly inhibited the immune response in both models, resulting in worse consequences for the host than those generated by single P. aeruginosa infection. Overall, the presence of M. abscessus produces a decline in the immune responses that worsens the infection and compromises the host.

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Section: Discussionmentioning

confidence: 99%

Interplay ofMycobacterium abscessusandPseudomonas aeruginosain coinfection: Biofilm Dynamics and Host Immune Response

Campo-Pérez,

Julián,

Torrents

2024

Preprint

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“…The Mabs 390R rough strain used in this study has been previously described (5,(15)(16)(17)(18)(19). It has been determined to be Mycobacterium abscessus subspecies abscessus (UT Health, The University of Texas Health Sciences Center at Tyler, Barbara A. Brown-Eliot).…”

Section: Bacteria and Lung Infectionmentioning

confidence: 99%

Mice with lung airway ciliopathy develop persistent Mycobacterium abscessus lung infection and have a proinflammatory lung phenotype associated with decreased T regulatory cells

Nava

Hahn²,

Wu³

et al. 2022

Front. Immunol.

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IntroductionHuman pulmonary infection with non-tuberculous mycobacteria (NTM) such as Mycobacterium abscessus (Mabs) occurs in seemingly immunocompetent patients with underlying structural lung disease such as bronchiectasis in which normal ciliary function is perturbed. In addition to alterations in mucociliary clearance, the local immunologic milieu may be altered in patients with structural lung disease, but the nature of these changes and how they relate to NTM persistence remain unclear.MethodsWe used a mouse strain containing a conditional floxed allele of the gene IFT88, which encodes for the protein Polaris. Deletion of this gene in adult mice reportedly leads to loss of cilia on lung airway epithelium and to the development of bronchiectasis. In a series of experiments, IFT88 control mice and IFT88 KO mice received different preparations of Mabs lung inocula with lung CFU assessed out to approximately 8 weeks post-infection. In addition, cytokine levels in bronchoalveolar lavage (BAL) fluid, lung T cell subset analysis, and lung histopathology and morphometry were performed at various time points.ResultsMabs embedded in agarose beads persisted in the lungs of IFT88 KO mice out to approximately 8 weeks (54 days), while Mabs agarose beads in the lungs of IFT88 control mice was cleared from the lungs of all mice at this time point. T cells subset analysis showed a decrease in the percentage of CD4+FoxP3+ T cells in the total lymphocyte population in the lungs of IFT88 KO mice relative to IFT88 control mice. Proinflammatory cytokines were elevated in the BAL fluid from infected IFT88 KO mice compared to infected IFT88 control mice, and histopathology showed an increased inflammatory response and greater numbers of granulomas in the lungs of infected IFT88 KO mice compared to the lungs of infected IFT88 control mice. Scanning lung morphometry did not show a significant difference comparing lung airway area and lung airway perimeter between IFT88 KO mice and IFT88 control mice.DiscussionPersistent lung infection in our model was established using Mabs embedded in agarose beads. The utility of using IFT88 mice is that a significant difference in Mabs lung CFU is observed comparing IFT88 KO mice to IFT88 control mice thus allowing for studies assessing the mechanism(s) of Mabs lung persistence. Our finding of minimal differences in lung airway area and lung airway diameter comparing IFT88 KO mice to IFT88 control mice suggests that the development of a proinflammatory lung phenotype in IFT88 KO mice contributes to Mabs lung persistence independent of bronchiectasis. The contribution of cilia to immune regulation is increasingly recognized, and our results suggest that ciliopathy associated with structural lung disease may play a role in NTM pulmonary infection via alteration of the local immunologic lung milieu.

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“…This cell line is hyporesponsive to TLR2/TLR1 receptor agonist and the rough MABS 390R strain. This SNP is likely to be present in the CF patient population ( Kempaiah et al, 2013 ). Paradoxically the presence of this SNP is protective against infection with Mycobacterium leprae ( Johnson et al, 2007 ).…”

Section: The Paradox Of Low Virulence and Ineffective Host Responsementioning

confidence: 99%

Mycobacterium abscessus: Shapeshifter of the Mycobacterial World

Ryan

Byrd

2018

Front. Microbiol.

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In this review we will focus on unique aspects of Mycobacterium abscessus (MABS) which we feel earn it the designation of “shapeshifter of the mycobacterial world.” We will review its emergence as a distinct species, the recognition and description of MABS subspecies which are only now being clearly defined in terms of pathogenicity, its ability to exist in different forms favoring a saprophytic lifestyle or one more suitable to invasion of mammalian hosts, as well as current challenges in terms of antimicrobial therapy and future directions for research. One can see in the various phases of MABS, a species transitioning from a free living saprophyte to a host-adapted pathogen.

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Cystic fibrosis CFBE41o‐ cells contain TLR1 SNP I602S and fail to respond to Mycobacterium abscessus

Cited by 6 publications

References 27 publications

Interplay ofMycobacterium abscessusandPseudomonas aeruginosain coinfection: Biofilm Dynamics and Host Immune Response

Interplay ofMycobacterium abscessusandPseudomonas aeruginosain coinfection: Biofilm Dynamics and Host Immune Response

Mice with lung airway ciliopathy develop persistent Mycobacterium abscessus lung infection and have a proinflammatory lung phenotype associated with decreased T regulatory cells

Mycobacterium abscessus: Shapeshifter of the Mycobacterial World

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