Wnt Signaling Regulates Macrophage Mediated Immune Response to Pathogens

Jati, Suborno; Sen, Malini

doi:10.5772/intechopen.86433

Cited by 6 publications

(7 citation statements)

References 75 publications

(126 reference statements)

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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%

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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%

“…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: 93%

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

2021

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“…In light of the demonstrated association of actin dynamics with Wnt5A signaling ( 9 , 17 , 36 ), we investigated if Wnt5A-assisted survival of the commensal bacteria is linked with actin assembly. Indeed, Wnt5A depletion-induced reduction in E. faecalis and L. rhamnosus survival in macrophages was clearly associated with diminution in actin assembly as demonstrated by confocal microscopy and subsequent ImageJ (intensity) analysis of phalloidin-stained cells ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Wnt5A Signaling Regulates Gut Bacterial Survival and T Cell Homeostasis

Sengupta

Jati

Maity

et al. 2022

mSphere

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Gut commensal bacterial diversity and T cell homeostasis are crucial entities of the host innate immune network, yet the molecular details of host-directed signaling pathways that sustain the steady state of gut bacterial colonization and T cell activation remain unclear. Here, we describe the protective role of a Wnt5A-actin axis in the survival of several gut bacterial commensals and its necessity in shaping gut bacterial colonization and the associated T cell repertoire.

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“…A Wnt5A-Actin axis supports the survival of commensal bacteria. In light of the demonstrated association of actin dynamics with Wnt5A signaling (9,17,32), we investigated if Wnt5A assisted survival of the commensal bacteria is linked with actin assembly. Indeed, Wnt5A depletion induced reduction in E. faecalis and L. rhamnosus survival in macrophages was clearly associated with diminution in actin assembly as demonstrated by confocal microscopy and subsequent ImageJ (intensity) analysis of phalloidin stained cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Wnt5A Signaling Regulates Gut Bacterial Survival and T cell Homeostasis

Sengupta

Jati

Maity

et al. 2022

Preprint

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In light of the demonstrated antagonism of Wnt5A signaling toward the growth of several bacterial pathogens, it was important to study the influence of Wnt5A on gut resident bacteria, and its outcome. Here we demonstrate that in contrast to inhibiting the survival of the established gut pathogen Salmonella enterica, Wnt5A clearly promotes the survival of the common gut commensals Enterococcus faecalis and Lactobacillus rhamnosus within macrophages through a self-perpetuating Wnt5A-Actin axis. A Wnt5A – Actin axis furthermore regulates the subsistence of the natural bacterial population of the Peyer’s patches, as is evident from the diminution in the countable bacterial colony forming units therein through the application of Wnt5A signaling and actin assembly inhibitors. Wnt5A dependency of the gut resident bacterial population is also manifested in the notable difference between the bacterial diversities associated with the feces and Peyer’s patches of Wnt5A heterozygous mice, which lack a functional copy of the Wnt5A gene, and the wild type counterparts. Alterations in gut commensal bacterial population resulting from either the lack of a copy of the Wnt5A gene or inhibitor mediated attenuation of Wnt5A signaling correlate with significantly different ratios of regulatory vs. activated CD4 T cells associated with the Peyer’s patches. Taken together, our study reveals the importance of Wnt5A signaling in shaping the gut commensal bacterial population and the T cell repertoire linked to it, thus unveiling a crucial control device for the maintenance of gut bacterial diversity and T cell homeostasis.Significance StatementGut commensal bacterial diversity and T cell homeostasis are crucial entities of the host innate immune network. Yet molecular details of host directed signaling pathways that sustain the steady state of gut bacterial colonization and T cell activation remain unclear. Here we describe the protective role of a Wnt5A-Actin axis in the survival of several gut bacterial commensals, and its importance in shaping gut bacterial colonization and the associated T cell repertoire. This study opens up new avenues of investigation into the role of the Wnt5A-Actin axis in protection of the gut from dysbiosis related inflammatory disorders.

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Wnt Signaling Regulates Macrophage Mediated Immune Response to Pathogens

Cited by 6 publications

References 75 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

Wnt5A Signaling Regulates Gut Bacterial Survival and T Cell Homeostasis

Wnt5A Signaling Regulates Gut Bacterial Survival and T cell Homeostasis

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