Mycobacterium intracellulare induces a Th17 immune response via M1-like macrophage polarization in canine peripheral blood mononuclear cells

Kim, Suji; Hyun, You-Seok; Park, Hong-Tae; Shin, Meong Cheol; Yoo, Han Sang

doi:10.1038/s41598-022-16117-2

Cited by 4 publications

(1 citation statement)

References 63 publications

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“…Leishmania is an important pathogen of dogs and both the DH82 cell line [53] as well as canine MDMs [54] were used to study the effect of Leishmania infection. Canine MDMs were also used to study Mycobacterium intracellulare infection, which polarized the MDM towards M1 [55]. Besides microorganisms changing polarization of macrophages, also communication between immune cells leading to polarization has been studied in which canine B-cells were able to switch M1 macrophages to M2 -like macrophages [56].…”

Section: Plos Onementioning

confidence: 99%

Characterization of polarization states of canine monocyte derived macrophages

Lyu,

Veldhuizen,

Ludwig

et al. 2023

PLoS ONE

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Macrophages can reversibly polarize into multiple functional subsets depending on their micro-environment. Identification and understanding the functionality of these subsets is relevant for the study of immune‑related diseases. However, knowledge about canine macrophage polarization is still in its infancy. In this study, we polarized canine monocytes using GM-CSF/IFN- γ and LPS towards M1 macrophages or M-CSF and IL-4 towards M2 macrophages and compared them to undifferentiated monocytes (M0). Polarized M1 and M2 macrophages were thoroughly characterized for morphology, surface marker features, gene profiles and functional properties. Our results showed that canine M1-polarized macrophages obtained a characteristic large, roundish, or amoeboid shape, while M2-polarized macrophages were smaller and adopted an elongated spindle-like morphology. Phenotypically, all macrophage subsets expressed the pan-macrophage markers CD14 and CD11b. M1-polarized macrophages expressed increased levels of CD40, CD80 CD86 and MHC II, while a significant increase in the expression levels of CD206, CD209, and CD163 was observed in M2-polarized macrophages. RNAseq of the three macrophage subsets showed distinct gene expression profiles, which are closely associated with immune responsiveness, cell differentiation and phagocytosis. However, the complexity of the gene expression patterns makes it difficult to assign clear new polarization markers. Functionally, undifferentiated -monocytes, and M1- and M2- like subsets of canine macrophages can all phagocytose latex beads. M2-polarized macrophages exhibited the strongest phagocytic capacity compared to undifferentiated monocytes- and M1-polarized cells. Taken together, this study showed that canine M1 and M2-like macrophages have distinct features largely in parallel to those of well-studied species, such as human, mouse and pig. These findings enable future use of monocyte derived polarized macrophages particularly in studies of immune related diseases in dogs.

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Section: Plos Onementioning

confidence: 99%

Characterization of polarization states of canine monocyte derived macrophages

Lyu,

Veldhuizen,

Ludwig

et al. 2023

PLoS ONE

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Response to treatment, relapse and outcome of two dogs treated for Mycobacterium avium infection

Coates,

Taylor,

D'Aout

et al. 2024

J of Small Animal Practice

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A 3‐year‐old male neutered Golden Retriever with nasal swelling and lymphadenopathy was diagnosed with diffuse Mycobacterium avium infection. Treatment with 9 months of enrofloxacin, clarithromycin and rifampicin was successful, but relapsed 10 months later with lymphadenopathy, skin plaques and testicular involvement. Repeat treatment for 12 months was effective but 15 months later a second relapse responded to the same therapy which is ongoing with survival from diagnosis of 82 months. A 1‐year‐old male neutered Portuguese Podengo was diagnosed with polyarthritis and M. avium infection and treated with enrofloxacin, clarithromycin and rifampicin for 4 months but relapsed, subsequently responding to combined pradofloxacin, rifampicin, doxycycline and ethambutol. After 12 months of treatment, M. avium was detected and treatment extended to 17 months before stopping when no organism was detected. Relapse occurred after 6 weeks, responding to retreatment but relapsing (polyarthropathy, lymphadenomegaly) after 15 months, with euthanasia 38 months after diagnosis. Dogs with M. avium are challenging to treat with frequent relapse; however, long‐term survival is possible.

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Immunologic features of nontuberculous mycobacterial pulmonary disease based on spatially resolved whole transcriptomics

Koh,

Kim,

Kim

et al. 2024

BMC Pulm Med

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Background The immunologic features of nontuberculous mycobacterial pulmonary disease (NTM-PD) are largely unclear. This study investigated the immunologic features of NTM-PD using digital spatial profiling techniques. Methods Lung tissues obtained from six patients with NTM-PD between January 1, 2006, and December 31, 2020, at Seoul National University Hospital were subjected to RNA sequencing. Cores from the peribronchial areas were stained with CD3, CD68, and DNASyto13, and gene expression at the whole-transcriptome level was quantified using PCR amplification and Illumina sequencing. Lung tissues from six patients with bronchiectasis collected during the same period were used as controls. The RNA sequencing results were validated using immunohistochemistry (IHC) in another cohort (30 patients with NTM-PD and 15 patients with bronchiectasis). Results NTM-PD exhibited distinct gene expression patterns in T cells and macrophages. Gene set enrichment analysis revealed that pathways related to antigen presentation and processing were upregulated in NTM-PD, particularly in macrophages. Macrophages were more prevalent and the expression of genes associated with the M1 phenotype (CD40 and CD80) was significantly elevated. Although macrophages were activated in the NTM-PD group T cell activity was unaltered. Notably, expression of the costimulatory molecule CD28 was decreased in NTM-PD. IHC analysis showed that T cells expressing Foxp3 or TIM-3, which facilitate the regulatory functions of T cells, were increased. Conclusions NTM-PD exhibits distinct immunologic signatures characterized by the activation of macrophages without T cell activation.

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Mycobacterium intracellulare induces a Th17 immune response via M1-like macrophage polarization in canine peripheral blood mononuclear cells

Cited by 4 publications

References 63 publications

Characterization of polarization states of canine monocyte derived macrophages

Characterization of polarization states of canine monocyte derived macrophages

Response to treatment, relapse and outcome of two dogs treated for Mycobacterium avium infection

Immunologic features of nontuberculous mycobacterial pulmonary disease based on spatially resolved whole transcriptomics

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