An integrated view of innate immune mechanisms in <i>C. elegans</i>

Harding, Benjamin W.; Ewbank, Jonathan J.

doi:10.1042/bst20210399

Cited by 15 publications

(8 citation statements)

References 115 publications

(100 reference statements)

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“…In this scenario, pals-22 or pals-25(Q293*) mutants have impaired cellular function, perhaps due to “free” PALS-25. The ORR/IPR may thus be activated downstream of such a ‘homeostasis altering molecular process’ (HAMP) [ 47 ]. There are several examples of IPR induction as a consequence of altered cellular homeostasis.…”

Section: Discussionmentioning

confidence: 99%

A pals-25 gain-of-function allele triggers systemic resistance against natural pathogens of C. elegans

et al. 2022

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Regulation of immunity throughout an organism is critical for host defense. Previous studies in the nematode Caenorhabditis elegans have described an “ON/OFF” immune switch comprised of the antagonistic paralogs PALS-25 and PALS-22, which regulate resistance against intestinal and epidermal pathogens. Here, we identify and characterize a PALS-25 gain-of-function mutant protein with a premature stop (Q293*), which we find is freed from physical repression by its negative regulator, the PALS-22 protein. PALS-25(Q293*) activates two related gene expression programs, the Oomycete Recognition Response (ORR) against natural pathogens of the epidermis, and the Intracellular Pathogen Response (IPR) against natural intracellular pathogens of the intestine. A subset of ORR/IPR genes is upregulated in pals-25(Q293*) mutants, and they are resistant to oomycete infection in the epidermis, and microsporidia and virus infection in the intestine, but without compromising growth. Surprisingly, we find that activation of PALS-25 seems to primarily stimulate the downstream bZIP transcription factor ZIP-1 in the epidermis, with upregulation of gene expression in both the epidermis and in the intestine. Interestingly, we find that PALS-22/25-regulated epidermal-to-intestinal signaling promotes resistance to the N. parisii intestinal pathogen, demonstrating cross-tissue protective immune induction from one epithelial tissue to another in C. elegans.

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Section: Discussionmentioning

confidence: 99%

A pals-25 gain-of-function allele triggers systemic resistance against natural pathogens of C. elegans

et al. 2022

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“…Nevertheless, we also noticed that, after 100% Xuebijing treatment, the expression of pmk-1 , daf-16 , bar-1 , dbl-1 , egl-1 , and elt-2 could not be recovered to control levels in PA14-infected nematodes ( Supplementary Figure S3 ), which is consistent with the limited effect observed in Figure 1B . The reason to examine the effect of insulin, p38 MAPK, Wnt, DBL-1/TGF-β, ELT-2, and PCD-related signals is that these 6 molecular signals are crucial and conserved during the control of innate immunity and stress response ( Kurz and Tan, 2004 ; Irazoqui et al, 2008 ; Arvanitis et al, 2013 ; Head et al, 2017 ; Wang, 2019 ; Harding and Ewbank, 2021 ). These 6 molecular signals are involved in the immunology of various diseases, such as diabetes, cancer, and hematologic disorders ( Rossini et al, 1985 ; Gao et al, 2015 ; Kim and Choi, 2015 ; Batlle and Massague, 2019 ; Galluzzi et al, 2019 ; Bertheloot et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Beneficial effect of Xuebijing against Pseudomonas aeruginosa infection in Caenorhabditis elegans

et al. 2022

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In the clinical intensive care units (ICU), the traditional Chinese medicine (TCM) formulation of Xuebijing has been frequently used for treating sepsis. Nevertheless, the underlying pharmacological mechanisms of Xuebijing remain largely unclear. Caenorhabditis elegans is an important experimental host for bacterial infections. Using C. elegans as an animal model, we here examined the potential of Xuebijing treatment against bacterial infection and the underlying mechanisms. Xuebijing treatment could inhibit the reduction tendency of lifespan caused by Pseudomonas aeruginosa infection. For the cellular mechanisms of this antibacterial infection property, we found that Xuebijing treatment rescued C. elegans lifespan to be against P. aeruginosa infection by inhibiting Pseudomonas colonization in the intestinal lumen. Meanwhile, the increase in the expression of antimicrobial genes induced by Pseudomonas infection was also suppressed by Xuebijing treatment. Moreover, the beneficial effect of Xuebijing against Pseudomonas infection depended on insulin, p38 MAPK, Wnt, DBL-1/TGF-β, ELT-2, and programmed cell death (PCD)-related signals. Although Xuebijing did not show obvious antibacterial activity, Xuebijing (100%) treatment could inhibit the Pseudomonas biofilm formation and decrease the expression of virulence genes (lasA, lasB, rhlA, rhlC, phzA, phzM, phzH, and phzS) and quorum sensing (QS)-related genes (lasI, lasR, rhlI, rhlR, pqsA, and pqsR). Our results support the potential role of Xuebijing treatment against bacterial infection in hosts.

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“…In this scenario, pals-22 or pals-25(Q293*) mutants have impaired cellular function, perhaps due to “free” PALS-25. The ORR/IPR may thus be activated downstream of such a ‘homeostasis altering molecular process’ (HAMP) [45]. There are several examples of IPR induction as a consequence of altered cellular homeostasis.…”

Section: Discussionmentioning

confidence: 99%

A pals-25 gain-of-function allele triggers systemic resistance against natural pathogens of C. elegans

Gang

Grover

Reddy

et al. 2022

Preprint

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Regulation of immunity throughout an organism is critical for host defense. Previous studies in the nematode Caenorhabditis elegans have described an "ON/OFF" immune switch comprised of the antagonistic paralogs PALS-25 and PALS-22, which regulate resistance against intestinal and epidermal pathogens. Here, we identify and characterize a PALS-25 gain-of-function mutant protein with a premature stop (Q293*), which we find is freed from physical repression by its negative regulator, the PALS-22 protein. PALS-25(Q293*) activates two related gene expression programs, the Oomycete Recognition Response (ORR) against natural pathogens of the epidermis, and the Intracellular Pathogen Response (IPR) against natural intracellular pathogens of the intestine. A subset of ORR/IPR genes is upregulated in pals-25(Q293*) mutants, and they are resistant to oomycete infection in the epidermis, and microsporidia and virus infection in the intestine, but without compromising growth. Surprisingly, we find that activation of PALS-25 seems to primarily stimulate the downstream bZIP transcription factor ZIP-1 in the epidermis, which leads to upregulation of gene expression in both the epidermis and in the intestine. Interestingly, we find that this epidermal-to-intestinal signaling promotes resistance to the N. parisii intestinal pathogen, demonstrating cross-tissue protective immune induction from one epithelial tissue to another in C. elegans.

show abstract

An integrated view of innate immune mechanisms in C. elegans

Cited by 15 publications

References 115 publications

A pals-25 gain-of-function allele triggers systemic resistance against natural pathogens of C. elegans

A pals-25 gain-of-function allele triggers systemic resistance against natural pathogens of C. elegans

Beneficial effect of Xuebijing against Pseudomonas aeruginosa infection in Caenorhabditis elegans

A pals-25 gain-of-function allele triggers systemic resistance against natural pathogens of C. elegans

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