Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria

The enormous number of commensal bacteria in the lower intestine of vertebrates share abundant molecular patterns used for innate immune recognition of pathogenic bacteria. We show that, even though commensals are rapidly killed by macrophages, intestinal dendritic cells (DCs) can retain small numbers of live commensals for several days. This allows DCs to selectively induce IgA, which helps protect against mucosal penetration by commensals. The commensal-loaded DCs are restricted to the mucosal immune compartment by the mesenteric lymph nodes, which ensures that immune responses to commensal bacteria are induced locally, without potentially damaging systemic immune responses.     

Reduction of intestinal carcinogen absorption by carcinogen-specific secretory immunity

A secretory immune response to the carcinogen 2-acetylaminofluorene (AAF) was elicited in rabbits by directly immunizing the small intestine with an AAF-cholera toxin conjugate. High-titer, high-affinity secretory immunoglobulin A (IgA) antibody to AAF was secreted into the intestinal lumen in response to this immunogen. Immune secretions reduced the transepithelial absorption of a 125I-labeled derivative of AAF by more than half. This reduction of absorption by hapten-specific IgA suggests that oral vaccines against carcinogens and toxicants could be developed for humans.     

Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria

The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn's disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases.     

小鼠鼻粘膜接种伤寒杆菌Fe-SOD的抗体应答

目的：观察小鼠鼻腔接种伤寒杆菌的Fe—SOD后血液和粘膜系统的抗体应答。方法：用IL-1作为佐剂,将伤寒杆菌的Fe—SOD经鼻腔接种小鼠,检测小鼠血液及肠液中的抗体应答。结果：当用IL-1作为佐剂时,经鼻腔接种伤寒杆菌Fe—SOD的小鼠血液和肠液中可产生高水平特异性IgG和IgA类抗体;而腹腔注射仅在血液中产生高水平特异性IgG抗体。结论：用IL-1作为佐剂,伤寒杆菌Fe—SOD经鼻腔接种后可引起小鼠粘膜系统和血液中的抗体应答。     

Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila

Although commensalism with gut microbiota exists in all metazoans, the host factors that maintain this homeostatic relationship remain largely unknown. We show that the intestinal homeobox gene Caudal regulates the commensal-gut mutualism by repressing nuclear factor kappa B-dependent antimicrobial peptide genes. Inhibition of Caudal expression in flies via RNA interference led to overexpression of antimicrobial peptides, which in turn altered the commensal population within the intestine. In particular, the dominance of one gut microbe, Gluconobacter sp. strain EW707, eventually led to gut cell apoptosis and host mortality. However, restoration of a healthy microbiota community and normal host survival in the Caudal-RNAi flies was achieved by reintroduction of the Caudal gene. These results reveal that a specific genetic deficiency within a host can profoundly influence the gut commensal microbial community and host physiology.     

Has the microbiota played a critical role in the evolution of the adaptive immune system?

Although microbes have been classically viewed as pathogens, it is now well established that the majority of host-bacterial interactions are symbiotic. During development and into adulthood, gut bacteria shape the tissues, cells, and molecular profile of our gastrointestinal immune system. This partnership, forged over many millennia of coevolution, is based on a molecular exchange involving bacterial signals that are recognized by host receptors to mediate beneficial outcomes for both microbes and humans. We explore how specific aspects of the adaptive immune system are influenced by intestinal commensal bacteria. Understanding the molecular mechanisms that mediate symbiosis between commensal bacteria and humans may redefine how we view the evolution of adaptive immunity and consequently how we approach the treatment of numerous immunologic disorders.     

Accelerated intestinal epithelial cell turnover: a new mechanism of parasite expulsion

The functional integrity of the intestinal epithelial barrier forms a major defense against invading pathogens, including gastrointestinal-dwelling nematodes, which are ubiquitous in their distribution worldwide. Here, we show that an increase in the rate of epithelial cell turnover in the large intestine acts like an "epithelial escalator" to expel Trichuris and that the rate of epithelial cell movement is under immune control by the cytokine interleukin-13 and the chemokine CXCL10. This host protective mechanism against intestinal pathogens has implications for our wider understanding of the multifunctional role played by intestinal epithelium in mucosal defense.     

感染法氏囊病毒雏鸡新城疫2次免疫后体液中Ig含量和HI抗体滴度变化

本文对1日龄人工感染传染性法氏囊病毒(IBDV)雏鸡2次新城疫免疫后血清、泪液、气管液、胆汁和肠液中免疫球蛋白(Ig)的含量和血清,泪液、气管液中血凝抑制抗体(HI)滴度进行了检测。结果表明,感染 IBDV 雏鸡 ND2次免疫后,其血清、泪液、气管液、胆汁和肠液中 IgM,IgG,IgA 含量及血清、泪液、气管液中 HI 抗体滴度均明显高于感染鸡1次 ND 免疫;但仍低于 ND2次免疫对照鸡。说明感染 IBDV 雏鸡 ND2次免疫,其全身如呼吸道、消化道局部的体液免疫应答水平较1次免疫明显升高,呈现免疫增强,但仍低于2次免疫对照组。提示IBDV 感染所致的雏鸡免疫抑制不是不可逆,但不可能完全恢复。     

监测重组蛋白EgM9免疫犬的特异性抗体变化

[目的]探索EgM家族重组蛋白(EgM 9)与Iscom为佐剂结合免疫犬后血清抗体变化规律.[方法]利用间接ELISA法检测免疫组与对照组血清特异性抗体(IgG、IgGi,IgG2,IgA、IgM和IgE)的变化规律,并以Western-blotting方法进行验证.[结果]经统计学方法分析显示,免疫组与对照组特异性抗体IgG及其亚类IgG1,IgG2,差异极显著(P <0.01),而特异性抗体IgA,IgM和IgE差异不显著(P > 0.05).[结论]证实EgM家族重组蛋白(EgM 9)与Iscom为佐剂结合能引起犬特异性免疫应答.     

雏鸡新城疫免疫后体液中Ig含量和HI滴度的动态变化

本研究对健康２周龄雏鸡ＮＤ免疫后血清、泪液、气管液、胆汁、肠液中ＩｇＭ，ＩｇＧ，ＩｇＡ含量和血清、泪液、气管液中ＨＩ抗体滴度进行了检测．结果表明，健康雏鸡１次ＮＤ免疫后其上述指标均升高，２次免疫后进一步升高．说明健康雏鸡ＮＤ免疫后，其全身和呼吸道、消化道局部都呈现明显的体液免疫应答，２次免疫后应答反应增强．     

Microbial exposure during early life has persistent effects on natural killer T cell function

Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma as compared with that of specific pathogen-free mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal-but not adult-GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.     

Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells

Normal intestinal mucosa contains abundant immunoglobulin A (IgA)-secreting cells, which are generated from B cells in gut-associated lymphoid tissues (GALT). We show that dendritic cells (DC) from GALT induce T cell-independent expression of IgA and gut-homing receptors on B cells. GALT-DC-derived retinoic acid (RA) alone conferred gut tropism but could not promote IgA secretion. However, RA potently synergized with GALT-DC-derived interleukin-6 (IL-6) or IL-5 to induce IgA secretion. Consequently, mice deficient in the RA precursor vitamin A lacked IgA-secreting cells in the small intestine. Thus, GALT-DC shape mucosal immunity by modulating B cell migration and effector activity through synergistically acting mediators.     

异丙酚对失血性休克大鼠小肠黏膜屏障功能的影响

目的观察异丙酚对失血性休克大鼠小肠黏膜屏障功能的影响。方法 36只雄性SD大鼠随机分为对照组和异丙酚组,制作失血性休克模型,经股静脉回输等量林格氏液,异丙酚组加用异丙酚5 mg/kg。18 h后处死大鼠,鲎试＋验测定血浆内毒素含量,免疫组化法检测小肠黏膜固有层IgA细胞,TUNEL法检测小肠黏膜细胞凋亡。结果与对照组＋比较,异丙酚组血浆内毒素含量明显减少,小肠黏膜上皮细胞凋亡指数明显降低,而小肠黏膜固有层IgA细胞数显著升高,差异均有统计学意义（P〈0.01）。结论异丙酚可保护失血性休克对大鼠小肠道黏膜屏障功能的损伤,减轻内毒素血症。     

PRRS弱毒株生殖道免疫对母猪阴道局部和全身IgA水平及特异性抗体水平的影响

猪繁殖与呼吸综合征(PRRS)弱毒株分别通过生殖道黏膜免疫和肌肉注射免疫母猪,再分别应用双夹心酶联免疫吸附试验(ELISA)技术检测阴道分泌物中分泌型免疫球蛋白A(SIgA)的水平和血液中免疫球蛋白A(IgA)水平,用竞争ELISA技术检测血液中PRRS特异性抗体的水平.结果表明:免疫后第3周,母猪生殖道免疫组阴道分泌物中SIgA水平显著高于对照组(P<0.05);血液IgA水平与对照组相比升高,但差异不显著;血液中PRRS特异性抗体水平与对照组相比也无显著差异.肌肉注射组母猪阴道分泌物中SIgA水平与对照组相比无显著差异.但血液中PRRS特异性抗体水平显著高于对照组(P<0.05).免疫后第5周生殖道免疫组阴道分泌物中SIgA水平和血液中IgA水平高于对照组,但无显著差异.肌肉注射组血液PRRS特异性抗体水平显著高于对照组(P<0.05).表明PRRS弱毒株经生殖道黏膜免疫能提高母猪生殖道局部SIgA的水平,但对血液中IgA和IgG水平影响不大.     

雏鸡对新城疫疫苗的免疫应答及其免疫保护机理

本实验共用240只1日龄健康雏鸡,分别于14,14和28日龄点眼滴鼻接种 Lasota 疫苗,在免疫后不同时期,采取实验鸡血液、泪液、肠液、气管液和胆汁、脾脏、法氏囊、胸腺、盲肠扁桃体、丕氏斑、十二指肠及哈德尔腺、支气管,检测了相应的 IgG,IgA,IgM 和 HI 滴度。T,B 细胞数量和功能,淋巴细胞数量以及浆细胞和酸性α-萘酚酯酶阳性 T 细胞(ANAE~+T)数量的动态变化。实验结果,雏鸡免疫后,脾脏、法氏囊和胸腺中 ANAR~+T 细胞与浆细胞显著增加,消化道和呼吸道相关局部免疫组织中的浆细胞、ANAE~+T 细胞数量也明显上升;与此相应,血液 T 细胞和脾脏 B 细胞免疫功能显著增强;血液 T,B 细胞、淋巴细胞数量显著升高;血清、泪液、气管液、胆汁和肠液中的 IgG,IgA,IgM 含量和 HI 滴度均程度不同地增加。免疫鸡脾脏、盲肠扁桃体和丕氏斑的淋巴小结数量增多,直径增大。这些表明免疫鸡不仅全身和局部的体液免疫反应,而且其细胞免疫应答也显著增强。雏鸡新城疫二免后,其免疫器官和局部免疫组织的浆细胞和 ANAE~+T 细胞进一步增多,血液 T 细胞和脾脏 B 细胞免疫功能也增强;血液 T 细胞。B 细胞与淋巴细胞数及 IgG,IgA,IgM含量和 HI 滴度程度不等地增加;泪液、气管液、肠液和胆汁的前述指标均升高,说明雏鸡 ND二免产生了显著的体液免疫和细胞免疫增强作用。新城疫强毒攻击后,对照鸡免疫器官组织和相应体液中的免疫指标均明显降低。呈现全身和局部免疫机能衰竭,全部死亡。与此相反,二免鸡免疫应答水平进一步提高,明显优于一免鸡,获得可靠的免疫保护,这与其显著增强的全身和局部细胞免疫和体液免疫反应密切相关。     

Immunological Changes of Chicks Immunized with March＇s Disease Vaccines and Challenged with Virulent MD Virus

ＩｍｍｕｎｏｌｏｇｉｃａｌＣｈａｎｇｅｓｏｆＣｈｉｃｋｓＩｍｍｕｎｉｚｅｄｗｉｔｈＭａｒｃｈ＇ｓＤｉｓｅａｓｅＶａｃｃｉｎｅｓａｎｄＣｈａｌｌｅｎｇｅｄｗｉｔｈＶｉｒｕｌｅｎｔＭＤＶｉｒｕｓ￥ＬｉｕＺｈｏｎｇｇｕｉ；ＧａｏＲｏｎｇ；ＬｉＱｉｎｇｚｈａ...     

Alleviating cancer drug toxicity by inhibiting a bacterial enzyme

The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial β-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial β-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial β-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11-induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy.     

益生菌在断奶仔猪日粮中的应用效果

为研究所制益生菌制剂在断奶仔猪中的应用效果,用以替代饲用抗生素,进行饲养试验,测定指标包括料重比、腹泻率,血清D乳酸、D木糖、IgA,肠道S IgA、绒毛高度、隐窝深度。结果表明益生菌制剂与饲用抗生素对断奶仔猪生长性能、生化指标、肠道形态学指标作用均差异不显著(P>0.05),但总体评价以添加益生菌制剂的试验2组效果较好。     

An alternative menaquinone biosynthetic pathway operating in microorganisms

In microorganisms, menaquinone is an obligatory component of the electron-transfer pathway. It is derived from chorismate by seven enzymes in Escherichia coli. However, a bioinformatic analysis of whole genome sequences has suggested that some microorganisms, including pathogenic species such as Helicobacter pylori and Campylobacter jejuni, do not have orthologs of the men genes, even though they synthesize menaquinone. We deduced the outline of this alternative pathway in a nonpathogenic strain of Streptomyces by bioinformatic screening, gene knockouts, shotgun cloning with isolated mutants, and in vitro studies with recombinant enzymes. As humans and commensal intestinal bacteria, including lactobacilli, lack this pathway, it represents an attractive target for the development of chemotherapeutics.