Wnt Signaling: Pathogen Incursion and Immune Defense

Jati, Suborno; Sarraf, Tresa Rani; Naskar, Debdut; Sen, Malini

doi:10.3389/fimmu.2019.02551

Cited by 22 publications

(24 citation statements)

References 88 publications

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“…In view of the role of Wnt5A signaling in actin assembly ( 16 , 24 , 27 , 28 ), we studied how the Wnt5A–Actin axis regulates the outcome of infection by a bacterial pathogen ( E. coli K1 isolate from a biliary sepsis patient) as compared to a non-pathogen (lab strain E. coli DH5α or E. coli K12-MG1655). The basis of pathogenicity and non-pathogenicity of these E. coli strains have already been documented ( 36 – 39 ).…”

Section: Discussionmentioning

confidence: 99%

“…Several labs including ours’ have demonstrated that Wnt5A signaling induces alterations in actin assembly in macrophages ( 16 , 24 , 27 , 28 ). This finding is in perfect agreement with the depicted role of Wnt5A in bacterial phagocytosis ( 15 ).…”

Section: Introductionmentioning

confidence: 92%

“…Several other bacteria, mostly non-pathogenic commensals are also able to reside in macrophages without being killed ( 22 , 23 ). Thus bacterial infections are inherently associated with the cytoskeletal actin dynamics of macrophages ( 24 – 26 ). However, despite considerable research and extensive knowledge in this field our understanding of how host defense mechanisms influence the cytoskeletal actin organization to regulate infection outcome remains incomplete.…”

Section: Introductionmentioning

confidence: 99%

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Wnt5A-Mediated Actin Organization Regulates Host Response to Bacterial Pathogens and Non-Pathogens

2021

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Wnt5A signaling facilitates the killing of several bacterial pathogens, but not the non-pathogen E. coli DH5α. The basis of such pathogen vs. non-pathogen distinction is unclear. Accordingly, we analyzed the influence of Wnt5A signaling on pathogenic E. coli K1 in relation to non-pathogenic E. coli K12-MG1655 and E. coli DH5α eliminating interspecies variability from our study. Whereas cell internalized E. coli K1 disrupted cytoskeletal actin organization and multiplied during Wnt5A depletion, rWnt5A mediated activation revived cytoskeletal actin assembly facilitating K1 eradication. Cell internalized E. coli K12-MG1655 and E. coli DH5α, which did not perturb actin assembly appreciably, remained unaffected by rWnt5A treatment. Phagosomes prepared separately from Wnt5A conditioned medium treated K1 and K12-MG1655 infected macrophages revealed differences in the relative levels of actin and actin network promoting proteins, upholding that the Wnt5A-Actin axis operates differently for internalized pathogen and non-pathogen. Interestingly, exposure of rWnt5A treated K1 and K12-MG1655/DH5α infected macrophages to actin assembly inhibitors reversed the scenario, blocking killing of K1, yet promoting killing of both K12-MG1655 and DH5α. Taken together, our study illustrates that the state of activation of the Wnt5A/Actin axis in the context of the incumbent bacteria is crucial for directing host response to infection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Wnt5A-Mediated Actin Organization Regulates Host Response to Bacterial Pathogens and Non-Pathogens

2021

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“…In brief, enriched GO terms characterized by upregulated DEGs were consistent with activation and mobilization of innate immune system factors, inflammation, host defense and wound healing. While prospective pathogen invasion pathways were connected to the downregulation of genes associated with wnt and integrin-mediated signaling as well as cell adhesion (59)(60)(61). GO categories were heavily enriched for downregulated genes in developmental process categories indicative of diverting metabolic resources away from growth.…”

Section: Local Host Responsementioning

confidence: 99%

Host-Parasite Interaction of Atlantic salmon (Salmo salar) and the Ectoparasite Neoparamoeba perurans in Amoebic Gill Disease

et al. 2021

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Marine farmed Atlantic salmon (Salmo salar) are susceptible to recurrent amoebic gill disease (AGD) caused by the ectoparasite Neoparamoeba perurans over the growout production cycle. The parasite elicits a highly localized response within the gill epithelium resulting in multifocal mucoid patches at the site of parasite attachment. This host-parasite response drives a complex immune reaction, which remains poorly understood. To generate a model for host-parasite interaction during pathogenesis of AGD in Atlantic salmon the local (gill) and systemic transcriptomic response in the host, and the parasite during AGD pathogenesis was explored. A dual RNA-seq approach together with differential gene expression and system-wide statistical analyses of gene and transcription factor networks was employed. A multi-tissue transcriptomic data set was generated from the gill (including both lesioned and non-lesioned tissue), head kidney and spleen tissues naïve and AGD-affected Atlantic salmon sourced from an in vivo AGD challenge trial. Differential gene expression of the salmon host indicates local and systemic upregulation of defense and immune responses. Two transcription factors, znfOZF-like and znf70-like, and their associated gene networks significantly altered with disease state. The majority of genes in these networks are candidates for mediators of the immune response, cellular proliferation and invasion. These include Aurora kinase B-like, rho guanine nucleotide exchange factor 25-like and protein NDNF-like inhibited. Analysis of the N. perurans transcriptome during AGD pathology compared to in vitro cultured N. perurans trophozoites, as a proxy for wild type trophozoites, identified multiple gene candidates for virulence and indicates a potential master regulatory gene system analogous to the two-component PhoP/Q system. Candidate genes identified are associated with invasion of host tissue, evasion of host defense mechanisms and formation of the mucoid lesion. We generated a novel model for host-parasite interaction during AGD pathogenesis through integration of host and parasite functional profiles. Collectively, this dual transcriptomic study provides novel molecular insights into the pathology of AGD and provides alternative theories for future research in a step towards improved management of AGD.

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“…Several other bacteria, mostly non-pathogenic commensals are also able to reside in macrophages without being killed (23,24). The idea one gets from several studies is that the fate of bacterial infections is associated with the cytoskeletal actin dynamics of macrophages (25)(26)(27). Despite considerable research in this field and extensive knowledge of the wide range of pathogenicity of several different bacteria our understanding of the molecular details of host macrophagebacteria interactions linked with infection outcome remains incomplete.…”

Section: Introductionmentioning

confidence: 99%

Host Response to Bacterial Pathogens and Non-Pathogens is Determined by Wnt5A Mediated Actin Organization

Jati

Sen

2020

Preprint

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Wnt5A signaling facilitates the killing of numerous bacterial pathogens but not non-pathogens. The basis of such distinction in killing remains unclear. Accordingly, we analyzed the influence of Wnt5A signaling on pathogenic E.coli K1 in relation to non-pathogenic E.coli K12-MG1655 and E.coli DH5α. We found that bacterial killing by macrophages is dictated by the effect of Wnt5A aided actin assembly on the incumbent bacteria. Actin assembly mediated by Wnt5A signaling antagonized the disruptive influence of internalized E.coli K1 on cytoskeletal actin facilitating its eradication. However, internalized E.coli K12-MG1655 and E.coli DH5α, which stabilize the actin cytoskleton remained unaffected by Wnt5A. Interestingly, actin assembly inhibitors altered bacterial phagosome compositions, supporting survival of K1, yet promoting killing of both K12-MG1655 and DH5α, in Wnt5A activated macrophages. Taken together, our study reveals the importance of Wnt5A signaling dependent assembly of cytoskeletal actin in determining the outcome of host response to bacterial pathogens and non-pathogens.

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Wnt Signaling: Pathogen Incursion and Immune Defense

Cited by 22 publications

References 88 publications

Wnt5A-Mediated Actin Organization Regulates Host Response to Bacterial Pathogens and Non-Pathogens

Wnt5A-Mediated Actin Organization Regulates Host Response to Bacterial Pathogens and Non-Pathogens

Host-Parasite Interaction of Atlantic salmon (Salmo salar) and the Ectoparasite Neoparamoeba perurans in Amoebic Gill Disease

Host Response to Bacterial Pathogens and Non-Pathogens is Determined by Wnt5A Mediated Actin Organization

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