Fumio Takizawa

Fukui Prefectural University · Faculty of Marine Science and Technology

Two types of adaptive immune strategies are known to have evolved in vertebrates: the VLR-based system, which is present in jawless organisms and is mediated by VLRA and VLRB lymphocytes, and the BCR/TCR-based system, which is present in jawed species and is provided by B and T cell receptors expressed on B and T cells, respectively. Here we summar...

Tetrapods contain a single CD4 coreceptor with four Ig domains that likely arose from a primordial two-domain ancestor. Notably, teleost fish contain two CD4 genes. Like tetrapod CD4, CD4-1 of rainbow trout includes four Ig domains, whereas CD4-2 contains only two. Because CD4-2 is reminiscent of the prototypic two-domain CD4 coreceptor, we hypothe...

Although mammalian secretory immunoglobulin A (sIgA) targets mucosal pathogens for elimination, its interaction with the microbiota also enables commensal colonization and homeostasis. This paradoxical requirement in the control of pathogens versus microbiota raised the question of whether mucosal (secretory) Igs (sIgs) evolved primarily to protect...

Germinal centers (GCs) or analogous secondary lymphoid microstructures (SLMs) are thought to have evolved in endothermic species. However, living representatives of their ectothermic ancestors can mount potent secondary antibody (Ab) responses upon infection or immunization, despite the apparent lack of SLMs in these cold-blooded vertebrates. How a...

The co-evolution between secretory immunoglobulins (sIgs) and microbiota began with the emergence of IgM over half a billion years ago. Yet, IgM function in vertebrates is mostly associated with systemic immunity against pathogens. sIgA and sIgT are the only sIgs known to be required in the control of microbiota homeostasis in warm- and cold-bloode...

The air-filled organs (AOs) of vertebrates (lungs and swim bladders) have evolved unique functions (air-breathing or buoyancy control in water) to adapt to different environments. Thus far, immune responses to microbes in AOs have been described exclusively in the lungs of tetrapods. Similar to lungs, swim bladders (SBs) represent a mucosal surface...

Generally speaking, cellular immune responses are comprised of innate and adaptive cell-based immune mechanisms in which all leukocyte subpopulations are involved. This includes effector functions such as phagocytosis, NETosis, and cell-mediated cytotoxicity. The main players are macrophages/monocytes, dendritic cells, granulocytes, NK cells, and c...

Kuchijirosho is a lethal infectious disease of fugu Takifugu rubripes, and the causative pathogen has been predicted to be an RNA virus. Although the homogenate of kuchijirosho-affected brain is pathogenic to fugu, the suspected viral particles have not been found in the brain and the viral genome has not been isolated. We attempted to clone the cD...

The skin of vertebrates is the outermost organ of the body and serves as the first line of defense against external aggressions. In contrast to mammalian skin, that of teleost fish lacks keratinization and has evolved to operate as a mucosal surface containing a skin-associated lymphoid tissue (SALT). Thus far, IgT representing the prevalent Ig in...

The skin of vertebrates is the outermost organ of the body and serves as the first line of defense against external aggressions. In contrast to mammalian skin, that of teleost fish lacks keratinization and has evolved to operate as a mucosal surface containing a skin-associated lymphoid tissue (SALT). Thus far, IgT representing the prevalent immuno...

Two genotypes of the intestinal parasite Ceratonova shasta infect Oncorhynchus mykiss: genotype 0 results in a chronic infection with low mortality while genotype IIR causes disease with high mortality. We determined parasite load and the relative expression of six immune factors (IgT, IgM, IL-6, IL-8, IL-10, IFNG) in fish infected with either geno...

Induction of adaptive immune responses in higher vertebrate species occur within organized lymphoid structures (e.g. lymph nodes, Peyer’s patches). It has been proposed that such structures emerged throughout evolutionary time with the goal to maximize encounters between antigens, antigens-presenting cells and B-T lymphocytes. Fish lack such struct...

Our previous work has shown the existence of distinct subsets of B cells in vertebrates that are highly phagocytic. To understand further the involvement of B cells in other potential innate immune functions, we performed the first comparative transcriptome analysis on FACS-sorted IgT+ and IgM+ B cells in rainbow trout, a primitive teleost fish spe...

The symbiosis between metazoans and prokaryotes is one of the most ancient and successful relationships found in nature. Mucosal surfaces are the main interface between animal hosts and their environment, and these surfaces are colonized by unique microbial communities that shape every physiological system of the host. Teleost fish have both an inn...

Chemokines and chemokine receptors have rapidly diversified in teleost fish but their immune functions remain unclear. We report in this study that 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, CK...

Ebola virus (EBOV) is a member of the Filoviridae family and the cause of hemorrhagic fever outbreaks. The EBOV VP40 (eVP40) matrix protein is the main driving force for virion assembly and budding. Indeed, expression of eVP40 alone in mammalian cells results in the formation and budding of virus-like particles (VLPs) which mimic the budding proces...

Commensal bacteria co-exist on the mucosal surfaces of all vertebrates. The host’s mucosal immune system must tolerate commensals while fighting pathogens. One of the mechanisms used by the mucosal immune system to maintain homeostasis is the secretion of immunoglobulins (Igs) across epithelial barriers, which is achieved via the polymeric immunogl...

Mucosal surfaces are the main route of entry for pathogens in all living organisms. In the case of teleost fish, mucosal surfaces cover the vast majority of the animal. As these surfaces are in constant contact with the environment, fish are perpetually exposed to a vast number of pathogens. Despite the potential prevalence and variety of pathogens...

Gas-exchange structures are critical for acquiring oxygen, but they also represent portals for pathogen entry. Local mucosal immunoglobulin responses against pathogens in specialized respiratory organs have only been described in tetrapods. Since fish gills are considered a mucosal surface, we hypothesized that a dedicated mucosal immunoglobulin re...

Supplementary Figures 1-11 and Supplementary References

A phenomenon already discovered more than 25 years ago is the possibility of naïve helper T cells to polarize into TH1 or TH2 populations. In a simplified model, these polarizations occur at opposite ends of an “immune 1-2 axis” (i1-i2 axis) of possible conditions. Additional polarizations of helper/regulatory T cells were discovered later, such as...

The 13th Congress of the International Society of Developmental and Comparative Immunology took place in Murcia Spain from June 28 to July 3, 2015 at the Victor Villegas Auditorium and Convention Center. There were two or three parallel sessions during the Congress that covered a wide range of immunological topics and brought researchers together f...

Interleukins 2 and 15 (IL-2 and IL-15) are highly differentiated but related cytokines with overlapping, yet also distinct functions, and established benefits for medical drug use. The present study identified a gene for an ancient third IL-2/15 family member in reptiles and mammals, interleukin 15-like (IL-15L), which hitherto was only reported in...

The investigation of the cellular immune response in fish species has been for a long time hampered by absence of appropriate monoclonal antibodies (MAbs) recognising subset specific surface markers. Consequently, the majority of immunological studies still focus on the changes in total leukocyte numbers or describe gene pattern in lymphoid organs...

Teleost fish express highly diverse naive TCRβ (TRB) repertoires and mount strong public and private clonal responses upon infection with pathogens. Fish T cells express typical markers such as CD8, CD4-1 and CD4-2, CD3, CD28 and CTLA4. Fish CD8(+) T cells have been shown to be responsible for antigen-specific cell-mediated cytotoxicity in in vitro...

Comparison of spectratype diversity index. A. ASD index distribution for S1 and S2 fractions from control group. The reference used is the average repertoire through both groups. B: ASD index distribution for S1 fractions from control and infected groups. The reference used is the average repertoire of control groups. C: ASD index distribution for...

Selected TRBV/C spectratypes from S1 and S2 T cell populations purified from control rainbow trout. (PDF)

Interferon gamma (IFNγ), a Th1-derived cytokine is one of the key molecules inducing cell-mediated immune responses in mammals. The expression of 2 distinct IFNγ (ifng1 and ifng2) and IFNγrel (ifngrel) genes was examined in kidney leukocytes from clonal ginbuna crucian carp Carassius auratus langsdorfii. The expression of IFNγ and IFNγrel genes was...

Ubiquitination regulates the activity, stability, and localization of a wide variety of proteins. Several mammalian MARCH ubiquitin E3 ligase proteins have been suggested to control cell surface immunoreceptors. The mitochondrial protein MARCH5 is a positive regulator of Toll-like receptor 7-mediated NF-κB activation in mammals. In the present stud...

The presence of helper and cytotoxic T cells in fish has been suggested, although T cell subsets have yet to be identified at the cellular level. In order to investigate the functions of CD4 and CD8α positive T cells we attempted to produce and characterize monoclonal antibodies (mAbs) against teleost CD4 and CD8α. Here we report the successful pro...

In teleost fish, a novel gene G6F-like was identified, encoding a type I transmembrane molecule with four extracellular Ig-like domains and a cytoplasmic tail with putative tyrosine phosphorylation motifs including YxN and an immunoreceptor tyrosine-based activation motif (ITAM). G6F-like maps to a teleost genomic region where stretches correspondi...

to be completed soon

CD8-positive (CD8(+)) cytotoxic T lymphocytes (CTL) have antigen-specific cytotoxic activity. In fish, however, CTL expressing CD8 on their cell surface have not been identified. In order to characterize the cells involved in specific cell-mediated cytotoxicity in teleosts, we separated and sorted ginbuna kidney leucocytes into CD8alpha(+), CD4(+)...

To characterise fish haematopoietic stem/progenitor cells, it is necessary to develop a culture system that supports proliferation and differentiation of these cells. In the present study, we established cell lines from various tissues of carp (Cyprinus carpio) and ginbuna (Carassius auratus langsdorfii). By using these cell lines, we developed a c...

Decoy receptor 3 (DcR3), a member of TNF receptor superfamily, is a soluble receptor without death domain and cytoplasmic domain, and secreted by cells and binds with FasL, LIGHT and TL1A. The principal function of DcR3 is the inhibition of apoptosis by the binding cytotoxic ligands. Expression of DcR3 has been reported in a wide array of normal hu...

We previously demonstrated that some fish have unique response in the form of reactive oxygen species (ROS) production. In the present study, we cloned and sequenced the full-length cDNAs for carp (Cyprinus carpio) phagocyte NADPH oxidase components: gp91phox, p22phox, p47phox, p67phox and p40phox. These amino acid sequences were compared with othe...

Cytokines are a group of proteins that are involved in a variety of immunological and inflammatory reactions. Recently, it has been reported that cytokine genes also play an important role during development in mammals. In fish, however, little is known about the role of immune-related genes during embryogenesis. Here, we report the mRNA expression...

On Apr 21, 2010 this sequence version replaced gi:196049291.

On Jan 12, 2010 this sequence version replaced gi:196049285.

We previously showed that side population (SP) cells, characterized by specific Hoechst dye efflux pattern in flow cytometric analysis, were present in teleost kidney hematopoietic tissue, and that kidney SP cells were enriched in hematopoietic stem cells (HSCs). ABCG2/Abcg2 is an ATP-binding cassette (ABC) transporter that is known to be associate...

GATA3, a transcriptional activator, plays a critical role in the development of T-cells and differentiation to T helper type 2 cells. To date, no information is available on the role of GATA3 in the teleost immune system. We identified full-length cDNA and alternatively spliced variants of ginbuna crucian carp GATA3 (gbGATA3). The gbGATA3 gene is t...

In the adaptive immune system of mammals, naive helper T (Th) cells differentiate into Th1 or Th2 cells. The T-box expressed in T cells (T-bet) is a member of a family of T-box transcription factors that regulates the expression of IFN-gamma and plays a crucial role in Th1 cell differentiation and cell-mediated immunity. We cloned and sequenced T-b...

Lck is a member of the Src-related protein tyrosine kinase family. In mammals, it is predominantly expressed in T cells, and plays crucial role in T-cell maturation and activation. In this report, the cloning, characterization, and expression analysis of lck genes from the S3n strain of ginbuna crucian carp Carassius auratus langsdorfii is describe...