Lineage relationship analysis of RORgammat+ innate lymphoid cells

Lymphoid tissue-inducer (LTi) cells initiate the development of lymphoid tissues through the activation of local stromal cells in a process similar to inflammation. LTi cells express the nuclear hormone receptor RORγt, which also directs the expression of the proinflammatory cytokine interleukin-17 in T cells. We show here that LTi cells are part of a larger family of proinflammatory RORγt(+) innate lymphoid cells (ILCs) that differentiate from distinct fetal liver RORγt(+) precursors. The fate of RORγt(+) ILCs is determined by mouse age, and after birth, favors the generation of cells involved in intestinal homeostasis and defense. Contrary to RORγt(+) T cells, however, RORγt(+) ILCs develop in the absence of microbiota. Our study indicates that RORγt(+) ILCs evolve to preempt intestinal colonization by microbial symbionts.     

CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance

Dendritic cells (DCs) and macrophages are critical to innate and adaptive immunity to the intestinal bacterial microbiota. Here, we identify a myeloid-derived mucosal DC in mice, which populates the entire lamina propria of the small intestine. Lamina propria DCs were found to depend on the chemokine receptor CX3CR1 to form transepithelial dendrites, which enable the cells to directly sample luminal antigens. CX3CR1 was also found to control the clearance of entero-invasive pathogens by DCs. Thus, CX3CR1-dependent processes, which control host interactions of specialized DCs with commensal and pathogenic bacteria, may regulate immunological tolerance and inflammation.     

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.     

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.     

A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria

The immunoglobulin A (IgA) is produced to defend mucosal surfaces from environmental organisms, but host defenses against the very heavy load of intestinal commensal microorganisms are poorly understood. The IgA against intestinal commensal bacterial antigens was analyzed; it was not simply "natural antibody" but was specifically induced and responded to antigenic changes within an established gut flora. In contrast to IgA responses against exotoxins, a significant proportion of this specific anti-commensal IgA induction was through a pathway that was independent of T cell help and of follicular lymphoid tissue organization, which may reflect an evolutionarily primitive form of specific immune defense.     

Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling

The symbiotic microbiota profoundly affect many aspects of host physiology; however, the molecular mechanisms underlying host-microbe cross-talk are largely unknown. Here, we show that the pyrroloquinoline quinone-dependent alcohol dehydrogenase (PQQ-ADH) activity of a commensal bacterium, Acetobacter pomorum, modulates insulin/insulin-like growth factor signaling (IIS) in Drosophila to regulate host homeostatic programs controlling developmental rate, body size, energy metabolism, and intestinal stem cell activity. Germ-free animals monoassociated with PQQ-ADH mutant bacteria displayed severe deregulation of developmental and metabolic homeostasis. Importantly, these defects were reversed by enhancing host IIS or by supplementing the diet with acetic acid, the metabolic product of PQQ-ADH.     

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.     

The ins and outs of body surface immunology

Rather than being confined to the secondary lymphoid tissue of the spleen and lymph nodes, large numbers of lymphocytes are intrinsically associated with the epithelial surfaces of the body. The best studied is gut-associated lymphoid tissue, but distinct epithelium-associated lymphoid tissue also exists in the reproductive tract, the lung, and the skin. The multiple cell types and functions composing these lymphoid tissues are increasingly seen as the key to how antigens delivered to body surfaces can elicit either immunogenic or tolerogenic responses. In some instances, these responses occur purely within the local body surface tissue, yet in other cases both local and systemic responses are elicited.     

Interleukin-22 drives endogenous thymic regeneration in mice

Endogenous thymic regeneration is a crucial function that allows for renewal of immune competence after stress, infection, or immunodepletion. However, the mechanisms governing this regeneration remain poorly understood. We detail such a mechanism, centered on interleukin-22 (IL-22) and triggered by the depletion of CD4(+)CD8(+) double-positive thymocytes. Intrathymic levels of IL-22 were increased after thymic insult, and thymic recovery was impaired in IL-22-deficient mice. IL-22, which signaled through thymic epithelial cells and promoted their proliferation and survival, was up-regulated by radio-resistant RORγ(t)(+)CCR6(+)NKp46(-) lymphoid tissue inducer cells after thymic injury in an IL-23-dependent manner. Administration of IL-22 enhanced thymic recovery after total body irradiation. These studies reveal mechanisms of endogenous thymic repair and offer innovative regenerative strategies for improving immune competence.     

Immune Responses of Chicken Immunized with Marek‘s Disease Vaccines

The experiment was conducted to study the dynamic changes of immune responses of chicks immunized with Marck‘s disease(MD) trivalent vaccine and turkey herpesvirus (HVT)at one day age.Results were found that after immunization of chicks with MD vaccines,the interlcukine-2 (IL-2) inductive activity and IL-2 receptor expression of T cells from thymus and spleen significantly increased.suggesting that the immunoregulative function was markedly enhanced in the immune organs;the number of antibody-producing cells,the number and proliferative function of T cells rose markedly in Bursa Fabricius,Splcen and thymus,indicating that the ccllular and humoral immune responses were elevated remarkablly in the central and peripheral immune organs; the number of T and antibody-producing cells as well as the content of IgG,IgA and IgM obviously mounted in cecal tonsil,Harder ian gland mucosal lymphoid tissucs of bronchus along with tears,trachea washings,bilc and intestinal fluids,demonstrating that the local and mucosal immunity was raised in the respiratory and digestive tract;the levels of immune responses mentioned above in the trivalent vaccine-immuniacd chicks were apparently higher than those of HVT-immunized birds.     

猪痢疾密螺旋体人工感染小鼠肠道的病理形态学观察

对人工感染猪痢疾密螺旋体的28只小鼠组织病理学观察表明:在感染后1-5天,小鼠肠道以渗出性炎症为主。具体表现为粘膜下层水肿,血管充血,腺腔扩张、杯状细胞稍有增生;在感染后7-30天转变为以固有层和粘膜下层淋巴细胞、浆细胞浸润孤立淋巴滤泡增生,生发中心增殖为主的变化。     

番鸭法氏囊相关淋巴组织的分布及组织学研究

研究了番鸭法氏囊柄部淋巴组织的分布及组织学结构。番鸭法氏囊柄部分布有多量的淋巴组织,以法氏囊柄的背侧淋巴组织分布面积最大、数量最多。其组织学结构包括淋巴相关上皮、上皮内淋巴细胞、圆顶区、淋巴滤泡以及高内皮静脉,其结构与其他粘膜相关淋巴组织相似。研究结果表明,分布于法氏囊柄部的淋巴组织是一种粘膜相关淋巴组织。     

Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora

Activation-induced cytidine deaminase (AID) plays an essential role in class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes. We report here that deficiency in AID results in the development of hyperplasia of isolated lymphoid follicles (ILFs) associated with a 100-fold expansion of anaerobic flora in the small intestine. Reduction of bacterial flora by antibiotic treatment of AID-/- mice abolished ILF hyperplasia as well as the germinal center enlargement seen in secondary lymphoid tissues. Because an inability to switch to immunoglobulin A on its own does not lead to a similar phenotype, these results suggest that SHM of ILF B cells plays a critical role in regulating intestinal microflora.     

Lymphoepithelial tissues of the intestine and differentiation of antibody production

The antibody response of young rabbits to the injection of killed Brucella abortus was abolished by prior extirpation of intestinal lymphoepithelial tissues combined with lethal xirradiation and reconstitution with rabbit fetal liver cells. Extirpative surgery alone, like lethal x-irradiation and reconstitution without surgery, did not abolish this response. Intestinal lymphoepithelial tissues of rabbits apparently play a central lymphoid function and are responsible for the differentiation of the lymphoid cell line which produces specific antibody and immunoglobulins.     

Successful transmission of a retrovirus depends on the commensal microbiota

To establish chronic infections, viruses must develop strategies to evade the host's immune responses. Many retroviruses, including mouse mammary tumor virus (MMTV), are transmitted most efficiently through mucosal surfaces rich in microbiota. We found that MMTV, when ingested by newborn mice, stimulates a state of unresponsiveness toward viral antigens. This process required the intestinal microbiota, as antibiotic-treated mice or germ-free mice did not transmit infectious virus to their offspring. MMTV-bound bacterial lipopolysaccharide triggered Toll-like receptor 4 and subsequent interleukin-6 (IL-6)-dependent induction of the inhibitory cytokine IL-10. Thus, MMTV has evolved to rely on the interaction with the microbiota to induce an immune evasion pathway. Together, these findings reveal the fundamental importance of commensal microbiota in viral infections.     

芽孢杆菌益生菌株的筛选

选用从健康动物肠道中分离的芽孢杆菌为出发菌株,按照益生菌的特定要求,模拟体内胆盐环境(胆盐含量0.3%w/v),来监测菌株的耐受能力;测定在人工胃液、肠液环境中作用不同时间后的存活率,初步筛选能够作为益生菌的芽孢杆菌。试验结果表明,有3株芽孢杆菌分别为:B5329、B22、B544,在胆酸盐、人工胃液、人工肠液中表现出了很强的耐受能力,其中B544还具有很强的产淀粉酶、蛋白酶和木聚糖酶的能力。     

Compartmentalized control of skin immunity by resident commensals

Intestinal commensal bacteria induce protective and regulatory responses that maintain host-microbial mutualism. However, the contribution of tissue-resident commensals to immunity and inflammation at other barrier sites has not been addressed. We found that in mice, the skin microbiota have an autonomous role in controlling the local inflammatory milieu and tuning resident T lymphocyte function. Protective immunity to a cutaneous pathogen was found to be critically dependent on the skin microbiota but not the gut microbiota. Furthermore, skin commensals tuned the function of local T cells in a manner dependent on signaling downstream of the interleukin-1 receptor. These findings underscore the importance of the microbiota as a distinctive feature of tissue compartmentalization, and provide insight into mechanisms of immune system regulation by resident commensal niches in health and disease.     

金黄色葡萄球菌攻击下小鼠泌乳期乳腺炎症病理机制分析

通过观察不同剂量(E1:10 CFU/μl;E2:20 CFU/μl;E3:100 CFU/μl;E4:200 CFU/μl;E5:2000CFU/μl)金黄色葡萄球菌攻击下的小鼠泌乳期乳腺炎症病理变化,选择最佳剂量建立小鼠乳腺内感染模型.结果表明:试验组乳腺组织中分离的细菌数呈先升高后下降的趋势,E3达到最高.组织形...