Zoccola Emmanuelle, Kellie Stuart, Barnes Andrew C
School of Biological Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia; Institute for Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia; Australian Institute for Infectious Diseases, The University of Queensland, St. Lucia, QLD 4072, Australia.
Mol Immunol. 2017 Mar;83:33-45. doi: 10.1016/j.molimm.2017.01.010. Epub 2017 Jan 15.
Fish represent the most diverse and abundant extant vertebrate infraclass. They are also one of the earliest divergent phyla with adaptive immunity based on antigen recognition by MHC and immunoglobulin. The aquaculture industry, which currently provides more than half of the fish for human consumption globally, has successfully exploited the adaptive immune system of fish through mass vaccination programs. However, vaccination against highly diverse antigens, mostly carbohydrates, such as capsular polysaccharides and lipopolysaccharide (LPS) is challenging. Fish have a subdued innate response to LPS, but adaptive response is generally high and type-specific. To better understand the link between initial innate response and early onset of adaptive immunity to carbohydrate antigens in the perciform barramundi (Lates calcarifer), an immune transcriptome was prepared from pronephros and spleen following vaccination with LPS and peptidoglycan. From 163,661 transcripts derived by Illumina mRNA-Seq, most grouped in neuronal, endocrine or immune system categories, suggesting a close relationship between the three systems. Moreover, digestive enzyme transcripts in spleen appeared to be highly inducible in barramundi. Most of the known TLRs were transcribed in the barramundi spleen and HK transcriptome, with the notable exception of TLR4, which is primarily responsible for LPS recognition in mammals. Several C-type lectin receptors were also identified, including CD209, CD205, and CLEC4E (Mincle). As Mincle has been shown to bind LPS and is abundant on dendritic cells, its role in response to LPS in barramundi was further investigated. A high dose of LPS induced TNF-alpha expression via Mincle. However, IL-6 regulation, whilst still regulated in response to LPS, did not depend upon the Mincle pathway, suggesting other routes of activation. This study thus suggests that Mincle acts as a partial substitute for TLR4 in barramundi in the processing of LPS.
鱼类是现存最多样化且数量最丰富的脊椎动物亚纲。它们也是最早分化出基于MHC和免疫球蛋白进行抗原识别的适应性免疫系统的门类之一。目前全球人类食用的鱼类有一半以上来自水产养殖业，该行业通过大规模疫苗接种计划成功利用了鱼类的适应性免疫系统。然而，针对高度多样化的抗原（大多为碳水化合物，如荚膜多糖和脂多糖（LPS））进行疫苗接种具有挑战性。鱼类对LPS的固有反应较弱，但适应性反应通常较强且具有类型特异性。为了更好地理解鲈形目尖吻鲈（Lates calcarifer）对碳水化合物抗原的初始固有反应与适应性免疫早期发作之间的联系，在用LPS和肽聚糖接种后，从肾脏和脾脏制备了免疫转录组。从Illumina mRNA-Seq获得的163,661个转录本中，大多数归类于神经、内分泌或免疫系统类别，表明这三个系统之间存在密切关系。此外，脾脏中的消化酶转录本在尖吻鲈中似乎具有高度诱导性。大多数已知的Toll样受体（TLR）在尖吻鲈脾脏和HK转录组中都有转录，但TLR4是个显著例外，它在哺乳动物中主要负责识别LPS。还鉴定出了几种C型凝集素受体，包括CD209、CD205和CLEC4E（小胶质细胞诱导型C型凝集素受体）。由于小胶质细胞诱导型C型凝集素受体已被证明可结合LPS且在树突状细胞上大量存在，因此进一步研究了其在尖吻鲈对LPS反应中的作用。高剂量的LPS通过小胶质细胞诱导型C型凝集素受体诱导肿瘤坏死因子-α（TNF-α）表达。然而，白细胞介素-6（IL-6）的调节虽然仍受LPS影响，但不依赖于小胶质细胞诱导型C型凝集素受体途径，这表明存在其他激活途径。因此这项研究表明，在尖吻鲈处理LPS的过程中，小胶质细胞诱导型C型凝集素受体起到了TLR4的部分替代作用。
