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Bacterial and fungal pattern recognition receptors in homologous innate signaling pathways of insects and mammals.

Stokes BA, Yadav S, Shokal U, Smith LC, Eleftherianos I - Front Microbiol (2015)

Bottom Line: Insect and mammalian innate immune receptors include molecules that recognize conserved microbial molecular patterns.Innate immune recognition leads to the recruitment of adaptor molecules forming multi-protein complexes that include kinases, transcription factors, and other regulatory molecules.Innate immune signaling cascades induce the expression of genes encoding antimicrobial peptides and other key factors that mount and regulate the immune response against microbial challenge.

View Article: PubMed Central - PubMed

Affiliation: Insect Infection and Immunity Laboratory, Department of Biological Sciences, The George Washington University Washington, DC, USA.

ABSTRACT
In response to bacterial and fungal infections in insects and mammals, distinct families of innate immune pattern recognition receptors (PRRs) initiate highly complex intracellular signaling cascades. Those cascades induce a variety of immune functions that restrain the spread of microbes in the host. Insect and mammalian innate immune receptors include molecules that recognize conserved microbial molecular patterns. Innate immune recognition leads to the recruitment of adaptor molecules forming multi-protein complexes that include kinases, transcription factors, and other regulatory molecules. Innate immune signaling cascades induce the expression of genes encoding antimicrobial peptides and other key factors that mount and regulate the immune response against microbial challenge. In this review, we summarize our current understanding of the bacterial and fungal PRRs for homologous innate signaling pathways of insects and mammals in an effort to provide a framework for future studies.

No MeSH data available.


Related in: MedlinePlus

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway in the fruit fly and the mouse. (A) The D. melanogaster JAK/STAT cytokine receptor, Domeless (Dome) is activated upon binding the Unpaired (Upd) cytokines, which causes the JAK tyrosine kinase Hopscotch (Hop) to phosphorylate itself and the cytoplasmic tail of Dome. The signal-transducer and activator of transcription at 92E (Stat92e) bind to the phosphotyrosines on the receptor, and are phosphorylated by Hop. Stat92e dissociate from the receptor, dimerize, move to the nucleus, and induce the transcription of Thioester-containing protein genes (Teps) and Turandot (Tot) stress genes. (B) In Mus musculus, interleukin-6 (IL-6) binds to its receptor (IL-6R) and activates the Glycoprotein GP130 via the JAK1/JAK2 kinases. STAT3 activation is dependent upon tyrosine phosphorylation, which induces dimerization via reciprocal phosphotyrosine-SH2 (Src homology domain 2) interaction between two STAT3 molecules. Activated STAT3 transcription factors translocate into the nucleus where they bind to consensus promoter sequences and cause the transcriptional induction of target genes, such as B-cell lymphoma-extra large (Bcl-xl), myeloid cell leukemia 1 (Mcl-1), cytochrome c oxidase II (Cox2), ILs [IL-6, IL-17, IL-23, Suppressor of cytokine signaling (Socs)].
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Figure 3: The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway in the fruit fly and the mouse. (A) The D. melanogaster JAK/STAT cytokine receptor, Domeless (Dome) is activated upon binding the Unpaired (Upd) cytokines, which causes the JAK tyrosine kinase Hopscotch (Hop) to phosphorylate itself and the cytoplasmic tail of Dome. The signal-transducer and activator of transcription at 92E (Stat92e) bind to the phosphotyrosines on the receptor, and are phosphorylated by Hop. Stat92e dissociate from the receptor, dimerize, move to the nucleus, and induce the transcription of Thioester-containing protein genes (Teps) and Turandot (Tot) stress genes. (B) In Mus musculus, interleukin-6 (IL-6) binds to its receptor (IL-6R) and activates the Glycoprotein GP130 via the JAK1/JAK2 kinases. STAT3 activation is dependent upon tyrosine phosphorylation, which induces dimerization via reciprocal phosphotyrosine-SH2 (Src homology domain 2) interaction between two STAT3 molecules. Activated STAT3 transcription factors translocate into the nucleus where they bind to consensus promoter sequences and cause the transcriptional induction of target genes, such as B-cell lymphoma-extra large (Bcl-xl), myeloid cell leukemia 1 (Mcl-1), cytochrome c oxidase II (Cox2), ILs [IL-6, IL-17, IL-23, Suppressor of cytokine signaling (Socs)].

Mentions: The Drosophila JAK/STAT cytokine receptor, Domeless (Dome), was identified through bipartite complementation assays showing that JAK homodimerization is abolished in the absence of Dome (Brown et al., 2003). Structural analysis characterized Dome as a transmembrane protein containing extracellular fibronectin type III domains with high homology to mammalian type I cytokine receptors of the interleukin-6 (IL-6) family, such as gp130 and IL-6R (Brown et al., 2001). The Unpaired (Upd) ligands are secreted upon injury or infection (Figure 3A). These glycosylated molecules were originally implicated in mutants that displayed small eyes and abnormal wing development phenotypes, but were later shown to induce tyrosine phosphorylation of Hop, the Drosophila homolog of JAK (Harrison et al., 1998). Loss-of-function Upd, Jak, and Stat mutants show similar phenotypes, leading to the conclusion that Upd molecules serve as the ligand for receptors that induce JAK/STAT signaling. Phosphorylation of the Stat92e transcription factors results in their dimerization and translocation into the nucleus where they bind to target sequences to induce effector gene expression. These include Turandot A (TotA) and complement-like thioester proteins, in insect hemocytes, that are dependent on Dome/upd3 signaling for expression (Lagueux et al., 2000; Agaisse et al., 2003).


Bacterial and fungal pattern recognition receptors in homologous innate signaling pathways of insects and mammals.

Stokes BA, Yadav S, Shokal U, Smith LC, Eleftherianos I - Front Microbiol (2015)

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway in the fruit fly and the mouse. (A) The D. melanogaster JAK/STAT cytokine receptor, Domeless (Dome) is activated upon binding the Unpaired (Upd) cytokines, which causes the JAK tyrosine kinase Hopscotch (Hop) to phosphorylate itself and the cytoplasmic tail of Dome. The signal-transducer and activator of transcription at 92E (Stat92e) bind to the phosphotyrosines on the receptor, and are phosphorylated by Hop. Stat92e dissociate from the receptor, dimerize, move to the nucleus, and induce the transcription of Thioester-containing protein genes (Teps) and Turandot (Tot) stress genes. (B) In Mus musculus, interleukin-6 (IL-6) binds to its receptor (IL-6R) and activates the Glycoprotein GP130 via the JAK1/JAK2 kinases. STAT3 activation is dependent upon tyrosine phosphorylation, which induces dimerization via reciprocal phosphotyrosine-SH2 (Src homology domain 2) interaction between two STAT3 molecules. Activated STAT3 transcription factors translocate into the nucleus where they bind to consensus promoter sequences and cause the transcriptional induction of target genes, such as B-cell lymphoma-extra large (Bcl-xl), myeloid cell leukemia 1 (Mcl-1), cytochrome c oxidase II (Cox2), ILs [IL-6, IL-17, IL-23, Suppressor of cytokine signaling (Socs)].
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4309185&req=5

Figure 3: The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway in the fruit fly and the mouse. (A) The D. melanogaster JAK/STAT cytokine receptor, Domeless (Dome) is activated upon binding the Unpaired (Upd) cytokines, which causes the JAK tyrosine kinase Hopscotch (Hop) to phosphorylate itself and the cytoplasmic tail of Dome. The signal-transducer and activator of transcription at 92E (Stat92e) bind to the phosphotyrosines on the receptor, and are phosphorylated by Hop. Stat92e dissociate from the receptor, dimerize, move to the nucleus, and induce the transcription of Thioester-containing protein genes (Teps) and Turandot (Tot) stress genes. (B) In Mus musculus, interleukin-6 (IL-6) binds to its receptor (IL-6R) and activates the Glycoprotein GP130 via the JAK1/JAK2 kinases. STAT3 activation is dependent upon tyrosine phosphorylation, which induces dimerization via reciprocal phosphotyrosine-SH2 (Src homology domain 2) interaction between two STAT3 molecules. Activated STAT3 transcription factors translocate into the nucleus where they bind to consensus promoter sequences and cause the transcriptional induction of target genes, such as B-cell lymphoma-extra large (Bcl-xl), myeloid cell leukemia 1 (Mcl-1), cytochrome c oxidase II (Cox2), ILs [IL-6, IL-17, IL-23, Suppressor of cytokine signaling (Socs)].
Mentions: The Drosophila JAK/STAT cytokine receptor, Domeless (Dome), was identified through bipartite complementation assays showing that JAK homodimerization is abolished in the absence of Dome (Brown et al., 2003). Structural analysis characterized Dome as a transmembrane protein containing extracellular fibronectin type III domains with high homology to mammalian type I cytokine receptors of the interleukin-6 (IL-6) family, such as gp130 and IL-6R (Brown et al., 2001). The Unpaired (Upd) ligands are secreted upon injury or infection (Figure 3A). These glycosylated molecules were originally implicated in mutants that displayed small eyes and abnormal wing development phenotypes, but were later shown to induce tyrosine phosphorylation of Hop, the Drosophila homolog of JAK (Harrison et al., 1998). Loss-of-function Upd, Jak, and Stat mutants show similar phenotypes, leading to the conclusion that Upd molecules serve as the ligand for receptors that induce JAK/STAT signaling. Phosphorylation of the Stat92e transcription factors results in their dimerization and translocation into the nucleus where they bind to target sequences to induce effector gene expression. These include Turandot A (TotA) and complement-like thioester proteins, in insect hemocytes, that are dependent on Dome/upd3 signaling for expression (Lagueux et al., 2000; Agaisse et al., 2003).

Bottom Line: Insect and mammalian innate immune receptors include molecules that recognize conserved microbial molecular patterns.Innate immune recognition leads to the recruitment of adaptor molecules forming multi-protein complexes that include kinases, transcription factors, and other regulatory molecules.Innate immune signaling cascades induce the expression of genes encoding antimicrobial peptides and other key factors that mount and regulate the immune response against microbial challenge.

View Article: PubMed Central - PubMed

Affiliation: Insect Infection and Immunity Laboratory, Department of Biological Sciences, The George Washington University Washington, DC, USA.

ABSTRACT
In response to bacterial and fungal infections in insects and mammals, distinct families of innate immune pattern recognition receptors (PRRs) initiate highly complex intracellular signaling cascades. Those cascades induce a variety of immune functions that restrain the spread of microbes in the host. Insect and mammalian innate immune receptors include molecules that recognize conserved microbial molecular patterns. Innate immune recognition leads to the recruitment of adaptor molecules forming multi-protein complexes that include kinases, transcription factors, and other regulatory molecules. Innate immune signaling cascades induce the expression of genes encoding antimicrobial peptides and other key factors that mount and regulate the immune response against microbial challenge. In this review, we summarize our current understanding of the bacterial and fungal PRRs for homologous innate signaling pathways of insects and mammals in an effort to provide a framework for future studies.

No MeSH data available.


Related in: MedlinePlus