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

Abstract

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.

Epigenetic Regulator miRNA Pattern Differences Among SARS-CoV, SARS-CoV-2, and SARS-CoV-2 World-Wide Isolates Delineated the Mystery Behind the Epic Pathogenicity and Distinct Clinical Characteristics of Pandemic COVID-19

“…To identify which pathways are associated with SARS-CoV and SARS-CoV infection, we have performed the gene ontology (GO) and pathway functional enrichment of the targeted genes using different tools. This revealed a myriad of significant functions and pathways involved in host immune responses, such as Wnt signaling (Ljungberg et al, 2019 ), MAPK signaling (Kimura et al, 2013 ), T-cell-mediated immunity (Channappanavar et al, 2014 ), autophagy (Yordy and Iwasaki, 2011 ), FGF receptor binding (van Asten et al, 2018 ), TGF-beta signaling (Denney et al, 2018 ), VEGF signaling (Alkharsah, 2018 ), ErbB signaling (Zheng et al, 2014 ), mTOR signaling (Le Sage et al, 2016 ), and TNF-alpha signaling (Kimura et al, 2013 ) are particularly targeted by SARS-CoV-2 ( Figures 7A–E ).…”

CD73+ CD127high Long-Term Memory CD4 T Cells Are Highly Proliferative in Response to Recall Antigens and Are Early Targets in HIV-1 Infection

“…We found that CD73+ CD4+ and CD8+ T cells include effector cells with high expression of TCF-1, which has also been demonstrated in murine quiescent memory T cells that are capable of proliferative responses in response to recall antigens [ 30 ]. TCF-1 is integral to Wnt/β-catenin signaling, but whether this signaling pathway is involved in memory T cell differentiation is still unclear [ 29 , 55 , 56 ]. High TCF-1 expression is also maintained during homeostatic proliferation [ 29 ], as we similarly found with maintenance of CD73 expression during IL-7 driven proliferation in vitro.…”

Epigenetic regulator miRNA pattern differences among SARS-CoV, SARS-CoV-2 and SARS-CoV-2 world-wide isolates delineated the mystery behind the epic pathogenicity and distinct clinical characteristics of pandemic COVID-19

“…To identify which pathways are associated with SARS-CoV and SARS-CoV infection, we have performed the gene ontology (GO) and pathway functional enrichment of the targeted genes using different tools. This reveals a myriad of significant functions and pathways involved in host immune responses, like-Wnt signaling (Ljungberg et al, 2019), MAPK signaling (Kimura et al, 2013), T cell-mediated immunity (Channappanavar et al, 2014), autophagy (Yordy and Iwasaki, 2011), FGF receptor binding (van Asten et al, 2018), TGF-beta signaling (Denney et al, 2018), VEGF signaling (Alkharsah, 2018), ErbB signaling (Zheng et al, 2014), mTOR signaling (Le Sage et al, 2016), TNF-alpha signaling (Kimura et al, 2013), etc are particularly targeted by SARS-CoV-2 (Figure 7A-7E).…”