Emerging role of macrophages in non-infectious diseases: An update

Yousaf, Hassan; Khan, Malik Ihsan Ullah; Ali, Iftikhar; Munir, Muhammad Usman; Lee, Ka Yiu

doi:10.1016/j.biopha.2023.114426

Cited by 12 publications

(2 citation statements)

References 150 publications

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“…Interestingly, several reports indicate a close relationship between the polarization of M2-like macrophages and elevated expression levels of IL-6 [ 58 – 60 ]. This phenomenon might be attributed to the complex and diverse regulatory mechanisms mediated by IL-6 in macrophages [ 61 , 62 ]. Further miRNA sequencing and Real-time RT-PCR analysis revealed that miRNA-222-3p may play a key role in the observed experimental results.…”

Section: Discussionmentioning

confidence: 99%

Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway

Zhang,

Wu,

Khan

et al. 2023

J Nanobiotechnol

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Objectives This study investigated whether exosomes from LPS pretreated bone marrow mesenchymal stem cells (LPS pre-MSCs) could prolong skin graft survival. Methods The exosomes were isolated from the supernatant of MSCs pretreated with LPS. LPS pre-Exo and rapamycin were injected via the tail vein into C57BL/6 mice allografted with BALB/c skin; graft survival was observed and evaluated. The accumulation and polarization of macrophages were examined by immunohistochemistry. The differentiation of macrophages in the spleen was analyzed by flow cytometry. For in vitro, an inflammatory model was established. Specifically, bone marrow-derived macrophages (BMDMs) were isolated and cultured with LPS (100 ng/ml) for 3 h, and were further treated with LPS pre-Exo for 24 h or 48 h. The molecular signaling pathway responsible for modulating inflammation was examined by Western blotting. The expressions of downstream inflammatory cytokines were determined by Elisa, and the polarization of macrophages was analyzed by flow cytometry. Results LPS pre-Exo could better ablate inflammation compared to untreated MSC-derived exosomes (BM-Exo). These loaded factors inhibited the expressions of inflammatory factors via a negative feedback mechanism. In vivo, LPS pre-Exo significantly attenuated inflammatory infiltration, thus improving the survival of allogeneic skin graft. Flow cytometric analysis of BMDMs showed that LPS pre-Exo were involved in the regulation of macrophage polarization and immune homeostasis during inflammation. Further investigation revealed that the NF-κB/NLRP3/procaspase-1/IL-1β signaling pathway played a key role in LPS pre-Exo-mediated regulation of macrophage polarization. Inhibiting NF-κB in BMDMs could abolish the LPS-induced activation of inflammatory pathways and the polarization of M1 macrophages while increasing the proportion of M2 cells. Conclusion LPS pre-Exo are able to switch the polarization of macrophages and enhance the resolution of inflammation. This type of exosomes provides an improved immunotherapeutic potential in prolonging graft survival.

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Section: Discussionmentioning

confidence: 99%

Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway

Zhang,

Wu,

Khan

et al. 2023

J Nanobiotechnol

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“…This is likely a consequence of the heterogeneity of the cochlear macrophage population following ototoxic trauma (Bedeir et al, 2022). Similarly, in other studies of macrophage involvement in trauma in the CNS (Chen et al, 2015) or non-infectious diseases generally (Yousaf et al, 2023), different macrophage types -e.g., M1 and M2 -can promote or reduce inflammation with consequent neurotoxic or neuroprotective consequences.…”

Section: Are Macrophages Detrimental or Beneficial To Sgn Survival?mentioning

confidence: 91%

Spiral ganglion neuron degeneration in aminoglycoside-deafened rats involves innate and adaptive immune responses not requiring complement

Gansemer,

Rahman,

Zhang

et al. 2024

Front. Mol. Neurosci.

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Spiral ganglion neurons (SGNs) transmit auditory information from cochlear hair cells to the brain. SGNs are thus not only important for normal hearing, but also for effective functioning of cochlear implants, which stimulate SGNs when hair cells are missing. SGNs slowly degenerate following aminoglycoside-induced hair cell loss, a process thought to involve an immune response. However, the specific immune response pathways involved remain unknown. We used RNAseq to gain a deeper understanding immune-related and other transcriptomic changes that occur in the rat spiral ganglion after kanamycin-induced deafening. Among the immune and inflammatory genes that were selectively upregulated in deafened spiral ganglia, the complement cascade genes were prominent. We then assessed SGN survival, as well as immune cell numbers and activation, in the spiral ganglia of rats with a CRISPR-Cas9-mediated knockout of complement component 3 (C3). Similar to previous findings in our lab and other deafened rodent models, we observed an increase in macrophage number and increased expression of CD68, a marker of phagocytic activity and cell activation, in macrophages in the deafened ganglia. Moreover, we found an increase in MHCII expression on spiral ganglion macrophages and an increase in lymphocyte number in the deafened ganglia, suggestive of an adaptive immune response. However, C3 knockout did not affect SGN survival or increase in macrophage number/activation, implying that complement activation does not play a role in SGN death after deafening. Together, these data suggest that both innate and adaptive immune responses are activated in the deafened spiral ganglion, with the adaptive response directly contributing to cochlear neurodegeneration.

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Accurate Diagnosis of Lower Respiratory Infections Using Host Response and Respiratory Microbiome from a Single Metatranscriptome Test of Bronchoalveolar Lavage Fluid

Zou,

Yan,

Wang

et al. 2024

Advanced Science

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Lower respiratory tract infections (LRTIs) diagnosis is challenging because noninfectious diseases mimic its clinical features. The altered host response and respiratory microbiome following LRTIs have the potential to differentiate LRTIs from noninfectious respiratory diseases (non‐LRTIs). Patients suspected of having LRTIs are retrospectively enrolled and a clinical metatranscriptome test is performed on bronchoalveolar lavage fluid (BALF). Transcriptomic and metagenomic analysis profiled the host response and respiratory microbiome in patients with confirmed LRTI (n = 126) or non‐LRTIs (n = 75). Patients with evidenced LRTIs exhibited enhanced pathways on chemokine and cytokine response, neutrophile recruitment and activation, along with specific gene modules linked to LRTIs status and key blood markers. Moreover, LRTIs patients exhibited reduced diversity and evenness in the lower respiratory microbiome, likely driven by an increased abundance of bacterial pathogens. Host marker genes are selected, and classifiers are developed to distinguish patients with LRTIs, non‐LRTIs, and indeterminate status, achieving an area under the receiver operating characteristic curve of 0.80 to 0.86 and validated in a subsequently enrolled cohort. Incorporating respiratory microbiome features further enhanced the classifier's performance. In summary, a single metatranscriptome test of BALF proved detailed profiles of host response and respiratory microbiome, enabling accurate LRTIs diagnosis.

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Emerging role of macrophages in non-infectious diseases: An update

Cited by 12 publications

References 150 publications

Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway

Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway

Spiral ganglion neuron degeneration in aminoglycoside-deafened rats involves innate and adaptive immune responses not requiring complement

Accurate Diagnosis of Lower Respiratory Infections Using Host Response and Respiratory Microbiome from a Single Metatranscriptome Test of Bronchoalveolar Lavage Fluid

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