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Cytokine/Chemokine Release Patterns and Transcriptomic Profiles of LPS/IFNγ-Activated Human Macrophages Differentiated with Heat-Killed Mycobacterium obuense , M-CSF, or GM-CSF.
- Source :
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International journal of molecular sciences [Int J Mol Sci] 2021 Jul 05; Vol. 22 (13). Date of Electronic Publication: 2021 Jul 05. - Publication Year :
- 2021
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Abstract
- Macrophages (Mφs) are instrumental regulators of the immune response whereby they acquire diverse functional phenotypes following their exposure to microenvironmental cues that govern their differentiation from monocytes and their activation. The complexity and diversity of the mycobacterial cell wall have empowered mycobacteria with potent immunomodulatory capacities. A heat-killed (HK) whole-cell preparation of Mycobacterium obuense ( M. obuense ) has shown promise as an adjunctive immunotherapeutic agent for the treatment of cancer. Moreover, HK M. obuense has been shown to trigger the differentiation of human monocytes into a monocyte-derived macrophage (MDM) type named Mob-MDM. However, the transcriptomic profile and functional properties of Mob-MDMs remain undefined during an activation state. Here, we characterized cytokine/chemokine release patterns and transcriptomic profiles of lipopolysaccharide (LPS)/interferon γ (IFNγ)-activated human MDMs that were differentiated with HK M. obuense (Mob-MDM(LPS/IFNγ)), macrophage colony-stimulating factor M-MDM(LPS/IFNγ)), or granulocyte/macrophage colony-stimulating factor (GM-MDM(LPS/IFNγ)). Mob-MDM(LPS/IFNγ) demonstrated a unique cytokine/chemokine release pattern (interleukin (IL)-10 <superscript>low</superscript> , IL-12/23p40 <superscript>low</superscript> , IL-23p19/p40 <superscript>low</superscript> , chemokine (C-x-C) motif ligand (CXCL)9 <superscript>low</superscript> ) that was distinct from those of M-MDM(LPS/IFNγ) and GM-MDM(LPS/IFNγ). Furthermore, M-MDM(LPS/IFNγ) maintained IL-10 production at significantly higher levels compared to GM-MDM(LPS/IFNγ) and Mob-MDM(LPS/IFNγ) despite being activated with M1-Mφ-activating stimuli. Comparative RNA sequencing analysis pointed to a distinct transcriptome profile for Mob-MDM(LPS/IFNγ) relative to both M-MDM(LPS/IFNγ) and GM-MDM(LPS/IFNγ) that comprised 417 transcripts. Functional gene-set enrichment analysis revealed significant overrepresentation of signaling pathways and biological processes that were uniquely related to Mob-MDM(LPS/IFNγ). Our findings lay a foundation for the potential integration of HK M. obuense in specific cell-based immunotherapeutic modalities such as adoptive transfer of Mφs (Mob-MDM(LPS/IFNγ)) for cancer treatment.
- Subjects :
- Cell Differentiation genetics
Cell Differentiation immunology
Granulocyte-Macrophage Colony-Stimulating Factor pharmacokinetics
Humans
Immunologic Factors pharmacology
In Vitro Techniques
Interferon-gamma pharmacology
Lipopolysaccharides pharmacology
Macrophage Activation drug effects
Macrophage Activation immunology
Macrophage Colony-Stimulating Factor pharmacology
Macrophages cytology
Macrophages metabolism
Transcriptome
Chemokines metabolism
Cytokines metabolism
Macrophages immunology
Nontuberculous Mycobacteria immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34281268
- Full Text :
- https://doi.org/10.3390/ijms22137214