An evolutionarily conserved program of B-cell development and activation in zebrafish

Page, Dawne M.; Wittamer, Valérie; Bertrand, Jean; Lewis, Kanako L.; Pratt, David; Delgado, Noemi; Schale, Sarah E.; McGue, Caitlyn; Jacobsen, Bradley H.; Doty, Alyssa; Pao, Yvonne; Yang, Hongbo; Neil, C.; Magor, Brad G.; Traver, David

doi:10.1182/blood-2012-12-471029

Cited by 178 publications

(174 citation statements)

References 49 publications

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“…AB*, Tg(lysC:DsRed2)nz50 , and Tg(flk1:ras-cherry) s896 zebrafish were mated, staged, and raised as previously described [24, 25]. All fish were raised and maintained under the guidelines of the University of California San Diego Institutional Animal Care and Use Committee guidelines.…”

Section: 1 Materials and Methodsmentioning

confidence: 99%

Streptococcus agalactiae infection in zebrafish larvae

Kim

Hancock

Cid

et al. 2015

Microbial Pathogenesis

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Streptococcus agalactiae (Group B Streptococcus, GBS) is an encapsulated, Gram-positive bacterium that is a leading cause of neonatal pneumonia, sepsis and meningitis, and an emerging aquaculture pathogen. The zebrafish (Danio rerio) is a genetically tractable model vertebrate that has been used to analyze the pathogenesis of both aquatic and human bacterial pathogens. We have developed a larval zebrafish model of GBS infection to study bacterial and host factors that contribute to disease progression. GBS infection resulted in dose dependent larval death, and GBS serotype III, ST-17 strain was observed as the most virulent. Virulence was dependent on the presence of the GBS capsule, surface anchored lipoteichoic acid (LTA) and toxin production, as infection with GBS mutants lacking these factors resulted in little to no mortality. Additionally, interleukin-1β il1b and CXCL-8 (cxcl8a) were significantly induced following GBS infection compared to controls. We also visualized GBS outside the brain vasculature, suggesting GBS penetration into the brain during the course of infection. Our data demonstrate that zebrafish larvae are a valuable model organism to study GBS pathogenesis.

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Section: 1 Materials and Methodsmentioning

confidence: 99%

Streptococcus agalactiae infection in zebrafish larvae

Kim

Hancock

Cid

et al. 2015

Microbial Pathogenesis

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“…From two to three weeks of age the adaptive immune system develops. [27][28][29] This is in contrast to mice and humans, where adaptive immune cells are present in the intestines during the first weeks of bacterial colonization. 30 Thus, the zebrafish model allowed us to specifically investigate the early bacterial colonization period in the absence of fully functional adaptive immunity and the impact of adaptive immune development on colonization thereafter.…”

Section: Introductionmentioning

confidence: 94%

T lymphocytes control microbial composition by regulating the abundance of Vibrio in the zebrafish gut

et al. 2014

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Abbreviations: wpf: weeks post fertilization.Dysbiosis of the intestinal microbial community is considered a risk factor for development of chronic intestinal inflammation as well as other diseases such as diabetes, obesity and even cancer. Study of the innate and adaptive immune pathways controlling bacterial colonization has however proven difficult in rodents, considering the extensive cross-talk between bacteria and innate and adaptive immunity. Here, we used the zebrafish to study innate and adaptive immune processes controlling the microbial community. Zebrafish lack a functional adaptive immune system in the first weeks of life, enabling study of the innate immune system in the absence of adaptive immunity. We show that in wild type zebrafish, the initial lack of adaptive immunity associates with overgrowth of Vibrio species (a group encompassing fish and human pathogens), which is overcome upon adaptive immune development. In Rag1-deficient zebrafish (lacking adaptive immunity) Vibrio abundance remains high, suggesting that adaptive immune processes indeed control Vibrio species. Using cell transfer experiments, we confirm that adoptive transfer of T lymphocytes, but not B lymphocytes into Rag1-deficient recipients suppresses outgrowth of Vibrio. In addition, ex vivo exposure of intestinal T lymphocytes to Rag1-deficient microbiota results in increased interferon-gamma expression by these T lymphocytes, compared to exposure to wild type microbiota. In conclusion, we show that T lymphocytes control microbial composition by effectively suppressing the outgrowth of Vibrio species in the zebrafish intestine.

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“…cDNA was prepared using QuantiTect Reverse Transcription Kit (Qiagen) and subjected to QRT-PCR with il-2rgc.a, il-2rgc.b, lck, ighm, and ef1a primers (37). Each primer set flanked splice sites such that amplification of contaminating genomic DNA would produce considerably larger fragments in each case.…”

Section: Rt-pcr Quantitative Rt-pcr and 59racementioning

confidence: 99%

Conserved IL-2Rγc Signaling Mediates Lymphopoiesis in Zebrafish

Sertori

Liongue

Basheer

et al. 2016

The Journal of Immunology

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The IL-2 receptor γ common (IL-2Rγc) chain is the shared subunit of the receptors for the IL-2 family of cytokines, which mediate signaling through JAK3 and various downstream pathways to regulate lymphopoiesis. Inactivating mutations in human IL-2Rγc result in SCID, a primary immunodeficiency characterized by greatly reduced numbers of lymphocytes. This study used bioinformatics, expression analysis, gene ablation, and specific pharmacologic inhibitors to investigate the function of two putative zebrafish IL-2Rγc paralogs, il-2rγc.a and il-2rγc.b, and downstream signaling components during early lymphopoiesis. Expression of il-2rγc.a commenced at 16 h post fertilization (hpf) and rose steadily from 4–6 d postfertilization (dpf) in the developing thymus, with il-2rγc.a expression also confirmed in adult T and B lymphocytes. Transcripts of il-2rγc.b were first observed from 8 hpf, but waned from 16 hpf before reaching maximal expression at 6 dpf, but this was not evident in the thymus. Knockdown of il-2rγc.a, but not il-2rγc.b, substantially reduced embryonic lymphopoiesis without affecting other aspects of hematopoiesis. Specific targeting of zebrafish Jak3 exerted a similar effect on lymphopoiesis, whereas ablation of zebrafish Stat5.1 and pharmacologic inhibition of PI3K and MEK also produced significant but smaller effects. Ablation of il-2rγc.a was further demonstrated to lead to an absence of mature T cells, but not B cells in juvenile fish. These results indicate that conserved IL-2Rγc signaling via JAK3 plays a key role during early zebrafish lymphopoiesis, which can be potentially targeted to generate a zebrafish model of human SCID.

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An evolutionarily conserved program of B-cell development and activation in zebrafish

Cited by 178 publications

References 49 publications

Streptococcus agalactiae infection in zebrafish larvae

Streptococcus agalactiae infection in zebrafish larvae

T lymphocytes control microbial composition by regulating the abundance of Vibrio in the zebrafish gut

Conserved IL-2Rγc Signaling Mediates Lymphopoiesis in Zebrafish

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