肠道卫士肥大细胞及其功能研究进展

肥大细胞(mast cells,MCs)的发育源于骨髓CD34^+前体细胞,肠道中MCs被激活后,可以释放多种生物活性介质,包括组胺、5-HT、类胰蛋白酶等.MCs因其独特的成熟特性和分泌颗粒的多样性在肠道固有和适应性免疫中均起到了至关重要的作用.多项研究表明,MCs与肠道的多种疾病密切相关,尤其以炎症性肠病、肠易激惹综合征和肠道过敏性疾病受到广泛关注.因此,肠道中MCs的功能及其作用机制在治疗临床相关疾病中的作用不可小觑.

Functional macrophages and gastrointestinal disorders

Macrophages(MΦ) differe ntiate from blood monocytes and participate in innate and adaptive immunity.Because of their abilities to recognize pathogens and activate bactericidal activities,MΦ are always discovered at the site of immune defense.MΦ in the intestine are unique,such that in the healthy intestine,they possess complex mechanisms to protect the gut from inflammation.In these complex mechanisms,they produce anti-inflammatory cytokines,such as interleukin-10 and transforming growth factor-β,and inhibit the inflammatory pathways mediated by Toll-like receptors.It has been demonstrated that resident MΦ play a crucial role in maintaining intestinal homeostasis,and they can be recognized by their unique markers.Nonetheless,in the inflamed intestine,the function of MΦ will change because of environmental variation,which may be one of the mechanisms of inflammatory bowel disease(IBD).We provide further explanation about these mechanisms in our review.In addition,we review recent discoveries that MΦ may be involved in the development of gastrointestinal tumors.We will highlight the possible therapeutic targets for the management of IBD and gastrointestinal tumors,and we also discuss why more details are needed to fully understand all other effects of intestinal MΦ.

Pichia pastoris composition expressed aerolysin mutant of Aeromonas veronii as an oral vaccine evaluated in zebrafish(Danio rerio)

Vaccines are one of the most practical means to stop the spreading of Aeromonas veronii in aquaculture.In this study,virulence factor aerolysin mutant NTaer which has lost its hemolytic activity was used as a target antigen.Pichia pastoris constitutive secretory expression NTaer(GS115-NTaer)was used as a potential safe oral vaccine to evaluate its effectiveness on zebrafish immunity.The result shows that vaccination of GS115-NTaer for four weeks did not affect the growth performance of the host,while eliciting an effective immune protective response.Compared with the control group,the GS115-NTaer could significantly up-regulate the relative expression level of the intestinal tight junction protein 1α(TJP1α)gene,and significantly increased the contents of lysozyme(LYZ),complement C3 and C4 in the gut,indicating that the innate immune response of the fish was activated.The relative gene expression levels of macrophage-expressed gene 1(MPEG1)and T cell receptor(TCR-α)in the gut,and MPEG1,CD4,CD8,TCR-α,GATA3,and T-bet in the spleen were all increased significantly,indicating that the cellular immune response of the fish was activated.Furthermore,the contents of serum IgM and intestinal mucosa IgZ antibodies were significantly increased,which showed that humoral immunity was also activated.Moreover,inoculation with GS115-NTaer significantly changed the structure of gut microbiota.In particular,the relative ratio of(Firmicutes+Fusobacteriota+Bacteroidota)/Proteobacteria was significantly higher than that of the control and GS115 groups.Lastly,the vaccinated fish were challenged with A.veronii,and the relative percent survival of GS115 and the GS115-NTear groups was 14.28%and 33.43%.This improvement of immunity was not only due to the specific immune response but also attributed to the improvement of innate immunity and the gut microbiota which was demonstrated by the germ-free zebrafish model.Collectively,this study provides information on the effectiveness of GS115-NTear as an oral vaccine for the green prevention and control of A.veronii infection in fish aquaculture.