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Aeromonas salmonicida Infection Only Moderately Regulates Expression of Factors Contributing to Toll-Like Receptor Signaling but Massively Activates the Cellular and Humoral Branches of Innate Immunity in Rainbow Trout (Oncorhynchus mykiss).

Brietzke A, Korytář T, Jaros J, Köllner B, Goldammer T, Seyfert HM, Rebl A - J Immunol Res (2015)

Bottom Line: In contrast, only the fish-specific tlr22a2 and the downstream factor irak1 featured clearly increased transcript levels, while the mRNA concentrations of many other tlr genes decreased.In conclusion, no specific TLR can be singled out as a dominant receptor for A. salmonicida.The recruitment of cellular factors of innate immunity rather than induced expression of pathogen receptors is hence of key importance for mounting a first immune defense against invading A. salmonicida.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute for Farm Animal Biology (FBN), Institute of Genome Biology, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.

ABSTRACT
Toll-like receptors (TLRs) are known to detect a defined spectrum of microbial structures. However, the knowledge about the specificity of teleost Tlr factors for distinct pathogens is limited so far. We measured baseline expression profiles of 18 tlr genes and associated signaling factors in four immune-relevant tissues of rainbow trout Oncorhynchus mykiss. Intraperitoneal injection of a lethal dose of Aeromonas salmonicida subsp. salmonicida induced highly increased levels of cytokine mRNAs during a 72-hour postinfection (hpi) period. In contrast, only the fish-specific tlr22a2 and the downstream factor irak1 featured clearly increased transcript levels, while the mRNA concentrations of many other tlr genes decreased. Flow cytometry quantified cell trafficking after infection indicating a dramatic influx of myeloid cells into the peritoneum and a belated low level immigration of lymphoid cells. T and B lymphocytes were differentiated with RT-qPCR revealing that B lymphocytes emigrated from and T lymphocytes immigrated into head kidney. In conclusion, no specific TLR can be singled out as a dominant receptor for A. salmonicida. The recruitment of cellular factors of innate immunity rather than induced expression of pathogen receptors is hence of key importance for mounting a first immune defense against invading A. salmonicida.

No MeSH data available.


Related in: MedlinePlus

Pathogen recognition in trout. Toll-like receptors, Nod1, and downstream factors as known from trout are listed with their GenBank accession numbers. Different colors of the LRR regions factors indicate the membership to individual Tlr families (TLR1 (blue), Tlr3 (orange), Tlr5 (black), Tlr7 (green), and Tlr11 (red)). Notably, a Tlr4 ortholog is absent in salmonid fish (marked with a flash). The Myddosome consisting of Myd88, Irak4a, and Irak1 (inside the green box) binds to the activated Tlr and recruits Traf6 and further downstream factors (indicated with a broken arrow), which in turn activate NF-κB. Tollip functionally inhibits Irak1 by preventing its recruitment into the Myddosome complex.
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fig1: Pathogen recognition in trout. Toll-like receptors, Nod1, and downstream factors as known from trout are listed with their GenBank accession numbers. Different colors of the LRR regions factors indicate the membership to individual Tlr families (TLR1 (blue), Tlr3 (orange), Tlr5 (black), Tlr7 (green), and Tlr11 (red)). Notably, a Tlr4 ortholog is absent in salmonid fish (marked with a flash). The Myddosome consisting of Myd88, Irak4a, and Irak1 (inside the green box) binds to the activated Tlr and recruits Traf6 and further downstream factors (indicated with a broken arrow), which in turn activate NF-κB. Tollip functionally inhibits Irak1 by preventing its recruitment into the Myddosome complex.

Mentions: Toll-like receptors (TLRs) are the best characterized innate immune receptors. More than 20 TLRs clustered in six subfamilies have been identified in more than a dozen of fish species [5–7] (Figure 1). They provide a wide spectrum for recognizing the plethora of aquatic pathogens. Upon ligand binding, TLRs dimerize and undergo conformational changes to recruit the Myddosome to the activated toll/interleukin-1 receptor domain (TIR) [8]. In mammals, this helical structure consists of six MYD88 (myeloid differentiation primary response protein 88) adaptor molecules, onto which a layer of four IRAK4 (interleukin-1 receptor-associated kinase 4) serine/threonine kinases and another layer of four IRAK2 or IRAK1 factors are assembled [8]. The composition of teleost Myddosome is unknown so far, although functional interaction of the complex Myd88-IRAK4a with the TIR domain has been reported [9]. However, no IRAK2 factor has yet been found in any teleostean fish species [5, 6].


Aeromonas salmonicida Infection Only Moderately Regulates Expression of Factors Contributing to Toll-Like Receptor Signaling but Massively Activates the Cellular and Humoral Branches of Innate Immunity in Rainbow Trout (Oncorhynchus mykiss).

Brietzke A, Korytář T, Jaros J, Köllner B, Goldammer T, Seyfert HM, Rebl A - J Immunol Res (2015)

Pathogen recognition in trout. Toll-like receptors, Nod1, and downstream factors as known from trout are listed with their GenBank accession numbers. Different colors of the LRR regions factors indicate the membership to individual Tlr families (TLR1 (blue), Tlr3 (orange), Tlr5 (black), Tlr7 (green), and Tlr11 (red)). Notably, a Tlr4 ortholog is absent in salmonid fish (marked with a flash). The Myddosome consisting of Myd88, Irak4a, and Irak1 (inside the green box) binds to the activated Tlr and recruits Traf6 and further downstream factors (indicated with a broken arrow), which in turn activate NF-κB. Tollip functionally inhibits Irak1 by preventing its recruitment into the Myddosome complex.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4525466&req=5

fig1: Pathogen recognition in trout. Toll-like receptors, Nod1, and downstream factors as known from trout are listed with their GenBank accession numbers. Different colors of the LRR regions factors indicate the membership to individual Tlr families (TLR1 (blue), Tlr3 (orange), Tlr5 (black), Tlr7 (green), and Tlr11 (red)). Notably, a Tlr4 ortholog is absent in salmonid fish (marked with a flash). The Myddosome consisting of Myd88, Irak4a, and Irak1 (inside the green box) binds to the activated Tlr and recruits Traf6 and further downstream factors (indicated with a broken arrow), which in turn activate NF-κB. Tollip functionally inhibits Irak1 by preventing its recruitment into the Myddosome complex.
Mentions: Toll-like receptors (TLRs) are the best characterized innate immune receptors. More than 20 TLRs clustered in six subfamilies have been identified in more than a dozen of fish species [5–7] (Figure 1). They provide a wide spectrum for recognizing the plethora of aquatic pathogens. Upon ligand binding, TLRs dimerize and undergo conformational changes to recruit the Myddosome to the activated toll/interleukin-1 receptor domain (TIR) [8]. In mammals, this helical structure consists of six MYD88 (myeloid differentiation primary response protein 88) adaptor molecules, onto which a layer of four IRAK4 (interleukin-1 receptor-associated kinase 4) serine/threonine kinases and another layer of four IRAK2 or IRAK1 factors are assembled [8]. The composition of teleost Myddosome is unknown so far, although functional interaction of the complex Myd88-IRAK4a with the TIR domain has been reported [9]. However, no IRAK2 factor has yet been found in any teleostean fish species [5, 6].

Bottom Line: In contrast, only the fish-specific tlr22a2 and the downstream factor irak1 featured clearly increased transcript levels, while the mRNA concentrations of many other tlr genes decreased.In conclusion, no specific TLR can be singled out as a dominant receptor for A. salmonicida.The recruitment of cellular factors of innate immunity rather than induced expression of pathogen receptors is hence of key importance for mounting a first immune defense against invading A. salmonicida.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute for Farm Animal Biology (FBN), Institute of Genome Biology, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.

ABSTRACT
Toll-like receptors (TLRs) are known to detect a defined spectrum of microbial structures. However, the knowledge about the specificity of teleost Tlr factors for distinct pathogens is limited so far. We measured baseline expression profiles of 18 tlr genes and associated signaling factors in four immune-relevant tissues of rainbow trout Oncorhynchus mykiss. Intraperitoneal injection of a lethal dose of Aeromonas salmonicida subsp. salmonicida induced highly increased levels of cytokine mRNAs during a 72-hour postinfection (hpi) period. In contrast, only the fish-specific tlr22a2 and the downstream factor irak1 featured clearly increased transcript levels, while the mRNA concentrations of many other tlr genes decreased. Flow cytometry quantified cell trafficking after infection indicating a dramatic influx of myeloid cells into the peritoneum and a belated low level immigration of lymphoid cells. T and B lymphocytes were differentiated with RT-qPCR revealing that B lymphocytes emigrated from and T lymphocytes immigrated into head kidney. In conclusion, no specific TLR can be singled out as a dominant receptor for A. salmonicida. The recruitment of cellular factors of innate immunity rather than induced expression of pathogen receptors is hence of key importance for mounting a first immune defense against invading A. salmonicida.

No MeSH data available.


Related in: MedlinePlus