Wnt5a contributes to dectin-1 and LOX-1 induced host inflammatory response signature in Aspergillus fumigatus keratitis

Che, Chengye; Cui, Li; Lin, Jing; Zhang, Jie; Jiang, Nan; Yuan, Kelan; Zhao, Guiqiu

doi:10.1016/j.cellsig.2018.08.020

Cited by 31 publications

(21 citation statements)

References 45 publications

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“…fumigatus, WNT5A expression was found to be significantly higher than in uninfected corneal tissues. WNT5A mRNA and protein expression were also enhanced by A. fumigatus infection of human THP-1 macrophages (78). Murine peritoneal macrophages infected with Candida albicans, A. fumigatus , or A. flavus or stimulated with the fungal and bacterial cell wall component Curdlan displayed elevated Wnt5a expression (79).…”

Section: Wnt Responses To Infectionmentioning

confidence: 99%

Functions of the WNT Signaling Network in Shaping Host Responses to Infection

et al. 2019

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It is well-established that aberrant WNT expression and signaling is associated with developmental defects, malignant transformation and carcinogenesis. More recently, WNT ligands have emerged as integral components of host responses to infection but their functions in the context of immune responses are incompletely understood. Roles in the modulation of inflammatory cytokine production, host cell intrinsic innate defense mechanisms, as well as the bridging of innate and adaptive immunity have been described. To what degree WNT responses are defined by the nature of the invading pathogen or are specific for subsets of host cells is currently not well-understood. Here we provide an overview of WNT responses during infection with phylogenetically diverse pathogens and highlight functions of WNT ligands in the host defense against infection. Detailed understanding of how the WNT network orchestrates immune cell functions will not only improve our understanding of the fundamental principles underlying complex immune response, but also help identify therapeutic opportunities or potential risks associated with the pharmacological targeting of the WNT network, as currently pursued for novel therapeutics in cancer and bone disorders.

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Section: Wnt Responses To Infectionmentioning

confidence: 99%

Functions of the WNT Signaling Network in Shaping Host Responses to Infection

et al. 2019

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“…According to in vivo and in vitro experiments, WNT5A was identified as a critical component of the antifungal immune response that can produce Dectin-1- and LOX-1-induced inflammatory signatures in response to A. fumigatus infection. 28 Caspase-12 may play an important role in the process of hypersensitivity to oxidative stress in keratoconus (KT) cornea fibroblasts. 29 Through analysis of gene expression profile data, GLDC was identified as playing a significant role in regulating various inflammatory processe s. 30 , 31 Aldehyde dehydrogenase (ALDH1A1) was found to be expressed in immature monocyte-derived dendritic cells; ALDH1A1 is an enzyme that contributes to the production of retinoic acid and is an important immunomodulator that regulates HIV-1 replication.…”

Section: Resultsmentioning

confidence: 99%

Section: Itgb2 Cfp Cyp2a5 Cybb Mmp9 Ccl9 Moxd1 Gabrp Igfbp3 mentioning

confidence: 99%

Transcriptome Analysis of the Gene Expression Profiles Associated with Fungal Keratitis in Mice Based on RNA-Seq

Zhang

Gong

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Fungal keratitis (FK) is an eye disease that can lead to blindness and has a high incidence worldwide. At present, there is no effective treatment for this disease. There are innate immune response mechanisms that protect against fungal infections. One example is C-type lectin receptors (CLRs), which can identify fungal invaders and trigger signal transduction pathways and cellular responses to eliminate pathogens. However, previous studies have focused mostly on single-receptor factors, and a systematic analysis of the genetic factors underlying the pathogenesis of FK has not been conducted. This study aimed to investigate the molecular mechanisms of FK in terms of genomics and to further elucidate its pathogenesis. METHODS. We performed a transcriptome analysis of a mouse model of FK using RNA sequencing to obtain the relevant gene expression profiles and to identify differentially expressed genes, signaling pathways, and regulatory networks of the key genetic factors in the pathogenesis of murine FK. RESULTS. Several genes that are significantly associated with FK and serve as markers of FK, such as the inflammatory cytokine genes IL1B, IL6, IL10, IL23, and TNF, were identified. The mRNA and protein expression patterns of IL-1β, IL-6, and TNF-α in the corneas of mice with FK were validated by quantitative RT-PCR and Luminex multiplex assay technology. The Wnt, cGMP-PKG, and Hippo signaling pathways were significantly enriched during fungal infection of mouse corneas. CONCLUSIONS. Our study may help to elucidate the mechanisms of FK pathogenesis and to identify additional candidate drug targets for the treatment of FK.

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“…Several lines of evidence substantiate that Wnt signaling, in particular Wnt5A signaling, is important for the cytoskeletal modulations and transcriptional programs inherent to macrophages during immune surveillance (3, 4, 6). While many pathogens are disabled through activation of Wnt5A signaling, some pathogens utilize it for their own survival within the host macrophage (3, 4, 7, 8, 65). Moreover, although not known exactly how, colonization of distinct microbiota within the lumen and macrophage associated niches within the gut and other anatomical locations correlate with differential expression of different Wnts and their signaling intermediates (9).…”

Section: Discussionmentioning

confidence: 99%

“…Similar to L. donovani infection, and unlike T. cruzi infection, fungal infection of macrophages by Aspergillus fumigatus is inhibited by Wnt5A signaling. Migration and accumulation of neutrophils caused by Erk1/2 and JNK mediated increase in production of Wnt5A after Dectin1/Lox1 assisted intracellular entry of the fungus have been identified as a cause for the fungal clearance (65). It is important to examine if secreted Wnt5A and actin alterations are directly involved in recruiting neutrophils and activating macrophages for phagocytic clearance of A. fumigatus .…”

Section: Interrelation Between Wnt Signaling and Infection With Pathomentioning

confidence: 99%

Wnt Signaling: Pathogen Incursion and Immune Defense

et al. 2019

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Wnt ligands interact with the transmembrane cell surface receptors Frizzled and ROR/RYK to initiate complex signaling cascades that are crucial for cell physiology and the proper functioning of the immune system. Wnt signaling is instrumental in maintaining immune surveillance and during infections by pathogenic microbes helps mount host resistance to infection. Some pathogens, however, utilize Wnt signaling to build a niche for their survival. The goal of this review is to summarize current and developing concepts about the tug of war between Wnt signaling and pathogens for deployment of host resources, focusing mostly on macrophages and cytoskeletal actin dynamics. An additional objective is to outline the interrelation between Wnt signaling and the host microbiota, which is vital for immune defense, discussing in the same perspective, how Wnt signaling could be differentiating pathogen from non-pathogen.

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Wnt5a contributes to dectin-1 and LOX-1 induced host inflammatory response signature in Aspergillus fumigatus keratitis

Cited by 31 publications

References 45 publications

Functions of the WNT Signaling Network in Shaping Host Responses to Infection

Functions of the WNT Signaling Network in Shaping Host Responses to Infection

Transcriptome Analysis of the Gene Expression Profiles Associated with Fungal Keratitis in Mice Based on RNA-Seq

Wnt Signaling: Pathogen Incursion and Immune Defense

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