Type I interferon signaling and macrophages: a double-edged sword?

Adler, Barbara; Adler, Heiko

doi:10.1038/s41423-020-00609-0

Cited by 8 publications

(6 citation statements)

References 9 publications

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“…Modules M5, M6 and M7 were tissue remodeling modules highly related to inflammatory fibroblasts and post-capillary venules. Interferon signaling module M4 was related to macrophage and post-capillary venules and was identified by previous studies 44,45 . The TNF-IR down-regulated cell type immature enterocytes 2 was highly related to lipid metabolism module M11.…”

Section: Relationship Between Anti-tnfα Molecular and Cellular Mechan...mentioning

confidence: 79%

The Clinical Response of Upadacitinib and Risankizumab is Associated with Reduced Inflammatory Bowel Disease Anti-TNFα Inadequate Response Mechanisms

Wang

Macoritto

Guay

et al. 2022

Preprint

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Background and Aims: JAK1 inhibitor upadacitinib and IL23 inhibitor risankizumab are efficacious in inflammatory bowel disease (IBD) patients who are anti-TNFα inadequate responders (TNF-IR). We aimed to understand the mechanisms mediating the response of upadacitinib and risankizumab. Methods: Eight tissue transcriptomic datasets from IBD patients treated with anti-TNFα therapies along with single-cell RNAseq data from ulcerative colitis were integrated to identify TNF-IR mechanisms. RNAseq colon tissue data from clinical studies of TNF-IR Crohn disease patients treated with upadacitinib or risankizumab were used to identify TNF-IR mechanisms that were favorably modified by upadacitinib and risankizumab. Results: We found seven TNF-IR up-regulated modules (M1-M7) related to innate/adaptive immune responses, interferon signaling and tissue remodeling, and five TNF-IR down-regulated modules (M8-M12) primarily related to metabolism. TNF-IR up-regulated cell types were inflammatory fibroblasts, post-capillary venules, inflammatory monocytes, macrophages, dendritic cells, and cycling B cells while subtypes of immature enterocytes, WNT5B+ cells and myofibroblasts were TNF-IR down-regulated cell types. Upadacitinib was associated with a significant decrease in the expression of most TNF-IR up-regulated modules in JAK1 responders (JAK1-R); in contrast, there was no change in these modules among TNF-IR patients treated with a placebo or among JAK1 inadequate responders (JAK1-IR). In addition, four of the six TNF-IR up-regulated cell types were significantly decreased after upadacitinib treatment in JAK1-R but not among subjects treated with a placebo or among JAK1-IR patients. We observed similar findings from colon biopsy samples from TNF-IR patients treated with risankizumab. Conclusions: Collectively, these data suggest that upadacitinib and risankizumab affect TNF-IR up-regulated mechanisms, which may account for their clinical response among TNF-IR IBD patients.

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Section: Relationship Between Anti-tnfα Molecular and Cellular Mechan...mentioning

confidence: 79%

The Clinical Response of Upadacitinib and Risankizumab is Associated with Reduced Inflammatory Bowel Disease Anti-TNFα Inadequate Response Mechanisms

Wang

Macoritto

Guay

et al. 2022

Preprint

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“…Type I IFNs are thought to have beneficial effects during viral infection, but this is not always the case in Mtb infection ( Moreira-Teixeira et al, 2018 ). Some studies have suggested dual pro- and anti-inflammatory properties of type I IFNs during Mtb infection in a time-dependent manner or in relation to type II IFNs ( Adler and Adler, 2021 ). Desvignes et al showed that mice lacking both the type I and type II IFN receptor genes, Ifnar and Ifngr , respectively, developed widespread granulomatous lesions, leading to early death, indicating a detrimental outcome of Mtb infection caused by disruption of both type I and type II IFNs ( Desvignes et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Transcription factor MAFB controls type I and II interferon response-mediated host immunity in Mycobacterium tuberculosis-infected macrophages

et al. 2022

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MAFB, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B, has been identified as a candidate gene for early tuberculosis (TB) onset in Thai and Japanese populations. Here, we investigated the genome-wide transcriptional profiles of MAFB-knockdown (KD) macrophages infected with Mycobacterium tuberculosis (Mtb) to highlight the potential role of MAFB in host immunity against TB. Gene expression analysis revealed impaired type I and type II interferon (IFN) responses and enhanced oxidative phosphorylation in MAFB-KD macrophages infected with Mtb. The expression of inflammatory chemokines, including IFN-γ-inducible genes, was confirmed to be significantly reduced by knockdown of MAFB during Mtb infection. A similar effect of MAFB knockdown on type I and type II IFN responses and oxidative phosphorylation was also observed when Mtb-infected macrophages were activated by IFN-γ. Taken together, our results demonstrate that MAFB is involved in the immune response and metabolism in Mtb-infected macrophages, providing new insight into MAFB as a candidate gene to guide further study to control TB.

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“…In the previous sections of this review, we have emphasized that caspase 1/4/5/11 specifically cleaved the linker between the amino-terminal gasdermin-N and carboxy-terminal gasdermin-C domains in GSDMD, which was required and sufficient for pyroptosis [ 109 , 241 ]. During microbial and parasitic infections, regulated cell death (RCD) [ 103 ] mediated by appropriate secretion of IFN-I [ 242 ] and activation of the inflammasome is vital for the host to cope with either foreign pathogens or tissue damage. Uncontrolled activities of these players can cause aberrant tissue damage, autoinflammatory disorders, cardiometabolic diseases, cancer and neurodegenerative diseases.…”

Section: Nod-like Receptors In the Regulation Of Pyroptosis Cell Deathmentioning

confidence: 99%

“…IFN-I was previously recognized as a crucial molecule that is involved in the protection against viral infections [ 243 , 244 ]; the current paradigm shift has shown its impact on a range of microbial infections, such as parasites, fungi and bacteria. Similar to cell death, IFN-I is also a double-edged sword that exhibits context-dependent functions in relation to the intrinsic and extrinsic factors in cells [ 242 , 245 ]. Protective host defense of IFN-I was demonstrated in Acinetobacter baumannii [ 246 ], Escherichia coli [ 247 ], Helicobacter pylori [ 91 ], Legionella pneumophila [ 248 ] Mycobacterium abscesssus [ 249 ], Plasmodium berghei [ 250 ] and Aspergillus species, A. fumigatus , A. nidulans and A. tanneri [ 251 ].…”

Section: Nod-like Receptors In the Regulation Of Pyroptosis Cell Deathmentioning

confidence: 99%

Nod-like Receptors: Critical Intracellular Sensors for Host Protection and Cell Death in Microbial and Parasitic Infections

Babamale

Chen

2021

IJMS

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Cell death is an essential immunological apparatus of host defense, but dysregulation of mutually inclusive cell deaths poses severe threats during microbial and parasitic infections leading to deleterious consequences in the pathological progression of infectious diseases. Nucleotide-binding oligomerization domain (NOD)-Leucine-rich repeats (LRR)-containing receptors (NLRs), also called nucleotide-binding oligomerization (NOD)-like receptors (NLRs), are major cytosolic pattern recognition receptors (PRRs), their involvement in the orchestration of innate immunity and host defense against bacteria, viruses, fungi and parasites, often results in the cleavage of gasdermin and the release of IL-1β and IL-18, should be tightly regulated. NLRs are functionally diverse and tissue-specific PRRs expressed by both immune and non-immune cells. Beyond the inflammasome activation, NLRs are also involved in NF-κB and MAPK activation signaling, the regulation of type I IFN (IFN-I) production and the inflammatory cell death during microbial infections. Recent advancements of NLRs biology revealed its possible interplay with pyroptotic cell death and inflammatory mediators, such as caspase 1, caspase 11, IFN-I and GSDMD. This review provides the most updated information that caspase 8 skews the NLRP3 inflammasome activation in PANoptosis during pathogen infection. We also update multidimensional roles of NLRP12 in regulating innate immunity in a content-dependent manner: novel interference of NLRP12 on TLRs and NOD derived-signaling cascade, and the recently unveiled regulatory property of NLRP12 in production of type I IFN. Future prospects of exploring NLRs in controlling cell death during parasitic and microbial infection were highlighted.

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Type I interferon signaling and macrophages: a double-edged sword?

Cited by 8 publications

References 9 publications

The Clinical Response of Upadacitinib and Risankizumab is Associated with Reduced Inflammatory Bowel Disease Anti-TNFα Inadequate Response Mechanisms

The Clinical Response of Upadacitinib and Risankizumab is Associated with Reduced Inflammatory Bowel Disease Anti-TNFα Inadequate Response Mechanisms

Transcription factor MAFB controls type I and II interferon response-mediated host immunity in Mycobacterium tuberculosis-infected macrophages

Nod-like Receptors: Critical Intracellular Sensors for Host Protection and Cell Death in Microbial and Parasitic Infections

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