CK12a, a CCL19-like Chemokine That Orchestrates both Nasal and Systemic Antiviral Immune Responses in Rainbow Trout

Abstract

Chemokines and chemokine receptors rapidly diversified in teleost fish but their immune functions remain unclear. We report here that Chemokine (C-C motif) ligand 19 (CCL19), a chemokine known to control lymphocyte migration and compartmentalization of lymphoid tissues in mammals, diversified in salmonids leading to the presence of six CCL19-like genes named CK10a, CK10b, CK12a, CK12b, CK13a and CK13b. Salmonid CCL19-like genes all contain the DCCL conserved motif but share low amino acid sequence identity. CK12 (but not CK10 or CK13) is constitutively expressed at high levels in all four trout MALT. Nasal vaccination with a live attenuated virus results in sustained up-regulation of CK12 (but not CK10 or CK13) expression in trout NALT. Trout recombinant CK12a (rCK12a) is not chemotactic in vitro but it increases the width of the nasal lamina propria (LP) when delivered intranasally (I.N.). rCK12a delivered I.N or i.p. stimulates the expression of CD8α, granulysin, and IFNγ in mucosal and systemic compartments and increases nasal CD8α+ cell numbers. rCK12a is able to stimulate proliferation of head kidney leucocytes (HKLs) from antigen experienced trout but not naïve controls yet it does not confer protection against viral challenge. These results show that local nasal production of CK12a contributes to antiviral immune protection both locally and systemically via stimulation of CD8 cellular immune responses and highlights a conserved role for CK12 in the orchestration of mucosal and systemic immune responses against viral pathogens in vertebrates.

Olfactory sensory neurons mediate ultra-rapid antiviral immune responses in teleosts in a TrkA-dependent manner

“…Histological changes in the OO were paralleled by changes in innate immune gene expression. Specifically, we observed a significant upregulation of ck10 , a CCL19-like chemokine in rainbow trout (Sepahi et al, 2017), and ptgs2b in OO 15 min after IHNV delivery. In the OB, in turn, we observed a significant downregulation in expression of ck10 and no significant change in expression of ptgs2b (Figure 4A).…”

“…We previously reported that nasal delivery of live attenuated IHNV results in the recruitment of myeloid and lymphoid cells to the local nasal environment 4 days after treatment in trout (Sepahi et al, 2017; Tacchi et al, 2014). Here, we report that leukocyte recruitment occurs as early as 15 min after IHNV delivery as visualized by the enlarged lamina propria (LP) of the olfactory lamellae of IHNV-treated fish compared to control fish (Figure S4A-C).…”

Interferon-stimulated genes in zebrafish and human define an ancient arsenal of antiviral immunity

“…* In humans and mice, ccl19 is implicated in lymphocyte migration and is important to define compartments within lymphoid tissues. In rainbow trout, one of the six ccl19 paralogues present in the genome participate to antiviral immunity though promotion of mucosal and central CD8+ T cell response (67).…”

Symbiont-derived sphingolipids regulate inflammatory responses in rainbow trout (Oncorhynchus mykiss)

“…The expression of IgM, IgT, IL-10, IL-1β, TGFβ-1a, TGFβ-1b and TNF-α was measured by RT-qPCR using specific primers (Table 2). qPCR was performed using 3μl cDNA template using specific primers as explained elsewhere (Sepahi, et al, 2017). Analysis was performed using the Pfaffl method (Pfaffl, 2001).…”