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1.
Host defense is an orchestrated response involving changes in the expression of receptors and release of mediators from both immune and structural cells. There is a growing recognition of the important role of proteolytic pathways for the protective immune response to enteric pathogens. Enteric nematode infection induces a type 2 immune response with polarization of macrophages toward the alternatively activated phenotype (M2). The Th2 cytokines, IL-4, and IL-13, induce a STAT6-dependent upregulation of the expression of the protease inhibitor, serpinB2, which protects macrophages from apoptosis. M2 are critical to worm clearance and a novel role for serpinB2 is its regulation of the chemokine, CCL2, which is necessary for monocyte and/or macrophage influx into small intestine during infection. There is a growing list of factors including immune (LPS, Th2 cytokines) as well as hormonal (gastrin, 5-HT) that are linked to increased expression of serpinB2. Thus, serpinB2 represents an immune regulated factor that has multiple roles in the intestinal mucosa.  相似文献   

2.
Infectious bursal disease virus (IBDV) is one of the most important infectious diseases of poultry around the world. Gut-associated lymphoid tissues (GALT) are the first line of defense of the host against the infection. The purpose of this study was to investigate the role of innate immune antiviral signaling triggered by Toll-like receptor 3 (TLR3), as well as macrophage activation and cytokine response in the intestinal lamina propria (ILP) cells after the oral challenge of IBDV in relation to IBDV virulence and disease pathogenesis. The results showed that the expression levels of TLR3, IRF7, IFN-α/β and the corresponding downstream antiviral factors OAS, PKR and Mx were all upregulated in the SPF chicken ILP cells at 8 h post-infection (hpi) and 12 hpi. Similarly, macrophages were activated, with the initial macrophage M1 activation observed at 8 hpi, but then it rapidly shifted to a non-protective M2-type. Both Th1 (IFN-γ, TNF-α, IL-12) and Th2 (IL-4 and IL-10) types of cytokines were differentially upregulated during the early stage of infection; however, the Th1 cytokines exhibited stronger activation before 8 hpi compared to those of the Th2 cytokines. Interestingly, differential regulations of gene expression induced by different IBDV strains with different virulence were detected. The HLJ0504-like very virulent (vv) IBDV strain NN1172 induced stronger activation of TLR3-IFN-α/β pathway, macrophages and the Th1/2 cytokines’ expression, compared to those induced by the attenuated strain B87 at 8 hpi and 12 hpi in the ILP cells. In conclusion, the innate antiviral response mediated by the TLR3-IRF7 pathway, macrophage activation and cytokine expression in the GALT cells at the early stage of IBDV infection was differentially modulated, and the HLJ0504-like vvIBDV strain triggered stronger activation than the attenuated vaccine strain, and that may play an important role in the progression of disease.  相似文献   

3.
There is growing evidence that helminth infections might suppress allergic responses by mechanisms potentially involving regulatory T lymphocytes, cytokines, helminth molecules and polyclonal IgE. Heligmosomoides polygyrus infection in mice is associated with reduced local and systemic immune responses, thus providing an excellent model to study the mechanisms of immune regulation. In this research, we examined the way that nematode infection modulates the influx of eosinophils into the airways of asthmatic mice. We observed a reduction in the total number and percentage of lung eosinophils that coincided with decreased levels of eotaxin in bronchoalveolar lavage fluid (BALF), lower expression of the CCR3 receptor on eosinophils and impaired chemotaxis of these cells toward eotaxin. We conclude that allergen-induced immune response was down-regulated as production of Th1 (IFN-gamma)-, Th2 (IL-4, IL-5)- and Treg (IL-10)-related cytokines as well as IL-6 and TNF-alpha was diminished upon nematode infection. We postulate that attenuation of allergic inflammation during H. polygyrus infection is a consequence of the dichotomy of the immune response in the face of concurrent antigenic challenge.  相似文献   

4.
Emerging role of IL-23/IL-17 axis in H pylori-associated pathology   总被引:2,自引:0,他引:2  
Colonization of stomach by H pylori is followed by a marked infiltration of the mucosa with polymorphonuclear leukocytes, macrophages, and lymphocytes that very often remains asymptomatic, but in some circumstances can lead to the development of gastroduodenal ulceration, gastric carcinoma, and mucosa-associated lymphoid tissue lymphoma. The molecular mechanisms by which Hpylori triggers and maintains the local immune response are complex, but there is evidence that cytokines produced by both immune and non-immune cells contribute to amplify the ongoing inflammation. H pylori infection is associated with a marked mucosal induction of T helper (Th) type 1 and Th17-type cytokines that is governed by specific antigen-presenting cell-derived molecules, such as interleukin (IL)-12 and IL-23. In this paper, we will review the available data on the expression and role of IL-23 and IL-17 in H pylori-related gastritis.  相似文献   

5.
目的 探究旋毛虫感染早期如何诱导肠道病理变化及免疫调节相关细胞因子表达情况。方法 通过苏木素伊红染色方法观察旋毛虫感染BALB/c鼠早期4个关键时间节点肠道病理学变化,采用电化学发光免疫分析法(Meso Scale Discovery,MSD)检测感染早期肠系膜淋巴结相关细胞因子表达情况。结果 肠道病理学结果表明,肠粘膜增厚,嗜酸性粒细胞浸润,数量明显增多。MSD结果显示,感染后6 h肠系膜淋巴结Th1型细胞因子(IL-2)表达水平显著降低,其他细胞因子无显著变化;感染后3 d至6 d,Th1型细胞因子(IL-2、IFN-γ)和Th2型细胞因子(IL-4、IL-10)表达水平均显著升高,呈Th1 / Th2混合型免疫应答。结论 旋毛虫感染后6 h至6 d肠道炎症随感染时间延长加重,感染后6 h Th1型免疫应答受到抑制,随后旋毛虫通过诱导机体产生以Th2型为主的混合型免疫应答,实现旋毛虫在机体内的长期寄生。  相似文献   

6.
Th1/Th2细胞因子与蠕虫感染   总被引:1,自引:0,他引:1  
蠕虫感染后引起复杂的免疫应答中辅助性T细胞处于核心位置,Th1/Th2细胞分泌的细胞因子在蠕虫感染后表达地位的不同,将决定蠕虫感染的发展与转归。本文对Th1/Th2细胞因子在蠕虫感染中的表达研究进展予以综述。  相似文献   

7.
Osteopontin (OPN) is a phosphorylated acidic glycoprotein that causes chemotaxis of macrophages and downregulation of nitric oxide synthesis. OPN has been shown to be involved in the pathogenesis of autoimmune diseases. Here, we tested the hypothesis that increased expression of pancreatic OPN in experimental diabetes has a protective role. The immune response phenotype associated with the induction of diabetes was evaluated in male OPN knockout (KO) and wild type (WT) mice. Multiple low dose streptozotocin (STZ) (MLDS), 40 mg/kg, was injected intraperitoneally for 5 days to establish a model for autoimmune diabetes. Glucose levels and body weight were evaluated in the vehicle and STZ treated groups. ELISA assay was used to monitor OPN serum levels in the WT diabetic mice. Histological studies evaluated insulitis development and Western blot analysis was employed to evaluate the expression levels of Th1 cytokines (TNF-alpha and IFN-gamma) and Th2 cytokines (IL-10 and IL-4). Immunohistochemistry was employed to localize IL-4 in the diabetic WT pancreata. Both WT and KO mice developed diabetes. In the WT, OPN serum levels were significantly upregulated 1 day after STZ injection. Pancreatic islets appeared larger in the KO group. Mild lymphocytic infiltrate and apoptosis were detected in the WT diabetic islets, while no signs of inflammation were detected in the KO group. WT diabetics showed upregulation of both Th1 and Th2 cytokines, whereas in the diabetic KO a mild upregulation of Th1 cytokines was detected with significant downregulation of IL-4. In the diabetic WT mice, IL-4 was localized in the interlobular connective tissue. Our studies show that the pancreatic immune response to MLDS diabetes is balanced between the Th1 and Th2 in the WT animals. KO mice show mild polarization towards the Th1 response. Although OPN is a known promoter for Th1 responses, it appears to have a regulatory control over the Th2 response in MLDS.  相似文献   

8.
9.
Basophils and mast cells are effecter cells in allergen/IgE-mediated immune responses. They induce type 1 immediate immune response in airway or other organ, resulting in bronchial asthma and other allergic diseases. However, they also play a critical role in host defense against infection with helminthes. Upon linkage of FcepsilonRI with a complex of allergen and IgE, basophils and mast cells release a large amount of Th2 cytokines and chemical mediators. Therefore these responses are "acquired allergic responses" and induce allergic diseases, such as bronchial asthma. However, basophils and mast cells derived from cultured bone marrow cells with IL-3 for 10 days express IL-18Ralpha chain and produce Th2 cytokines in response to the stimulation with IL-3 and IL-18 without FcepsilonRI cross-linkage. Furthermore, they produce Th2 cytokines upon stimulation with several TLR ligands, such as LPS. This finding may suggest the presence of allergen/IgE-independent allergic responses, which we would like to designate as "innate allergic response". However, in vivo treatment with IL-18 and IL-2 protects against gastrointestinal nematode infection by activating intestinal mucosal mast cells in STAT6-independent manner, suggesting the importance of innate allergic response against helminth infection. Here we discuss the functional role of IL-18-induced "innate allergic response" in disease and host defense.  相似文献   

10.
As an animal model, rat schistosomiasis mansoni has provided considerable knowledge of immune mechanisms involved in the expulsion of worms and in a subsequent development of immunity to reinfection. Although it is clear that ADCC mechanisms participate in immunity to reinfection; the nature of the cytokines involved in immunity is unknown. To analyse the pattern of cytokines involved, the mRNA levels of different cytokines were assessed by RT-PCR as they occur within tissues during the course of infection. In spleens from infected rats, a significant elevation in IL-2 and IL-5 mRNA was observed during the early phase of infection (day 7). Analysis of pulmonary cytokine responses showed a dramatic increase in IL-4 and IL-5 on day 7. This was accompanied with a low but significant increase in IL-2 (day 11) and IL-12 (day 7) in the absence of augmented IFN-γ expression. The cytokine expression patterns of draining lymph nodes (LN) from infected rats showed a significant increase of IL-2, IL-4 and IL-5 on day 21. Analysis of IL-10 expression showed exclusively a significant increase in LN on day 11. IFN-γ mRNA was not detected in any tissue sample. Thus, rats develop a predominately Th2-type cytokine response during a primary infection which may be involved at least in part, in the expression of immunity against Schistosoma mansoni infection .  相似文献   

11.
目的 观察日本血吸虫感染小鼠肝肉芽肿病变与一氧化氮 (NO)、Th1/Th2细胞因子水平的动态变化 ,探讨NO介导Th1/Th2免疫偏移在血吸虫卵肉芽肿病变中的作用。方法 采用石蜡切片 ,HE染色后观察感染小鼠肉芽肿病变。用硝酸还原酶法和ELISA夹心法分别检测日本血吸虫感染小鼠 0~ 12周血清及脾CD+ 4 T淋巴细胞培养上清NO、IFNγ和IL - 4表达水平 ,并进行相关分析。结果 感染小鼠 0~ 12周血清和脾CD+ 4 T淋巴细胞培养上清NO表达水平与小鼠肝肉芽肿病变动态相一致 ,并呈显著正相关 ,与IFNγ表达水平呈显著正相关 ,而与IL - 4在小鼠感染慢性期 (12周 )呈显著负相关。结论 NO在日本血吸虫感染小鼠肝肉芽肿病变过程中可能是一种与Th1/Th2细胞因子具有同样重要作用的调节因子 ,并可能是通过调节Th1/Th2细胞因子而发挥作用的 ,通过调控NO合成介导Th1/Th2免疫偏移可能是控制血吸虫卵肉芽肿病变的新途径  相似文献   

12.
Interleukin (IL)-12 is a multifunctional cytokine acting as a key regulator of cell-mediated immune responses through the differentiation of naïve CD4+ T cells into type 1 helper T cells (Th1) producing interferon-γ. As our knowledge of IL-12 family members is rapidly growing, it will be important to specify their involvement in the regulation of mycobacterial infection. This article is a review of the current knowledge regarding the functions of the IL-12 family cytokines in the immune host defense system against mycobacteria. Specifically, this review aims to describe recent scientific evidence concerning the protective role of some members of the IL-12 family cytokines for the control of mycobacterial infection, as well as to summarize knowledge of the potential use of the IL-12 family members as potent adjuvants in the prevention and treatment of mycobacterial infectious diseases. In addition, recent data supporting the importance of the IL-12 family members in mycobacterial diseases in relation to Th17 function are discussed. This examination will help to improve our understanding of the immune response to mycobacterial infection and also improve vaccine design and immunotherapeutic intervention against tuberculosis.  相似文献   

13.
The M2 subset of macrophages has a critical role to play in host tissue repair, tissue fibrosis and modulation of adaptive immunity during helminth infection. Infection with the helminth, Fasciola hepatica, is associated with M2 macrophages in its mammalian host, and this response is mimicked by its excretory‐secretory products (FhES). The tegumental coat of F. hepatica (FhTeg) is another major source of immune‐modulatory molecules; we have previously shown that FhTeg can modulate the activity of both dendritic cells and mast cells inhibiting their ability to prime a Th1 immune response. Here, we report that FhTeg does not induce Th2 immune responses but can induce M2‐like phenotype in vivo that modulates cytokine production from CD4+ cells in response to anti‐CD3 stimulation. FhTeg induces a RELMα expressing macrophage population in vitro, while in vivo, the expression of Arg1 and Ym‐1/2 but not RELMα in FhTeg‐stimulated macrophages was STAT6 dependent. To support this finding, FhTeg induces RELMα expression in vivo prior to the induction of IL‐13. FhTeg can induce IL‐13‐producing peritoneal macrophages following intraperitoneal injection This study highlights the important role of FhTeg as an immune‐modulatory source during F. hepatica infection and sheds further light on helminth–macrophage interactions.  相似文献   

14.
BackgroundHupB is an iron-regulated protein essential for the growth of Mycobacterium tuberculosis inside macrophages. To investigate if HupB induced a dominant Th2 type immune response, we studied the effect of rHupB on PBMCs from TB patients and by infecting mouse macrophages with wild type and hupB KO mutants.MethodsPBMCs from pulmonary TB (n = 60), extra pulmonary TB (n = 23) and healthy controls (n = 30) were stimulated with purified HupB and the cytokines secreted were assayed. The sera were screened for anti-HupB antibodies by ELISA. Mouse macrophages cell line (RAW 264.7) was infected with wild type, hupB KO and hupB-complemented strains of M. tuberculosis grown in high and low iron medium and the expression of cytokines was assayed by qRT-PCR.ResultsMurine macrophages infected with the hupB KO strain produced low levels of the pro-inflammatory cytokines IFN-γ, TNF-α, IL-1, and IL-18 and high levels of IL-10. HupB induced IL-6 and IL-10 production in PBMCs of TB patients and down-regulated IFN-γ and TNF-α production. The influence of HupB was remarkable in the EPTB group.ConclusionHupB shifted the immune response to the Th2 type. Low IFN-γ and elevated IL-10 in EPTB patients is noteworthy.  相似文献   

15.
Recently, we demonstrated a novel role for gastrointestinal mast cells (MCs) in the early events that lead to the generation of Th2 immunity to helminth infection. ( 1) Mice lacking MCs (Kit (W) /Kit (W-v) and Kit (W-Sh) ) showed a significant inhibition of Th2 cell priming following infection with the parasitic helminth Heligmosomoides polygyrus bakeri (Hp). We showed that MCs degranulate during the early stages of infection when the helminth larvae invade the small intestinal tissue. Furthermore, MC degranulation was required for the enhanced expression and production of the tissue-derived cytokines IL-25, IL-33 and TSLP, which are required for the optimal orchestration and priming of type 2 immunity. In this addendum we aim to address several questions raised by our findings - in particular, the mechanisms through which MCs may recognize helminth exposure in the early stages of infection and by which they may enhance expression of critical tissue cytokines thus, enabling Th2 priming. Furthermore, we will discuss these findings in the context of recently described novel innate immune cells, such as type 2 hematopoietic progenitors and type 2 innate lymphoid cells.  相似文献   

16.
目的 探讨巨噬细胞在感染结核分支杆菌后氮氧化物(NO)的产生和细胞因子表达的差异,了解结核感染的免疫应答过程,探讨死菌苗作为新的结核候选疫苗的可行性。方法 用ELISA和RT-PCR方法比较研究巨噬细胞在感染结核分支杆菌后NO的产生和细胞因子表达的差异。结果 活的结核分支杆菌H37Rv能显诱导巨噬细胞产生NO、IL-1、IL-12、IL-18、TNF-α以及iNOS的表达。细菌数对NO的产生和细胞因子的表达也有很大的影响。结论 活的结核分支杆菌H37Rv能显诱导巨噬细胞产生。NO和细胞因子,而产生有利于宿主的免疫应答。同样量的死结核分支杆菌H37Rv不能显诱导巨噬细胞产生NO和细胞因子,不宜作为新的结核候选疫苗。  相似文献   

17.
Respiratory syncytial virus (RSV) is a single-stranded negative sense RNA virus in the Paramyxovirus family that is a major cause of morbidity and life-threatening lower respiratory tract disease in infants and young children worldwide. RSV is recognized as a ubiquitous virus having considerable worldwide disease burden. Studies investigating the immune response and disease pathogenesis associated with infection attribute the interplay of the virus with host factors, particularly cytokines and chemokines, in inflammation, disease, and immune effector processes. There is convincing evidence that Th1- and Th2-type cytokine patterns determine the type of immune response to RSV infection, and that the spectrum of cytokine expression affects control mechanisms involved in the regulation of disease pathogenesis and chronicity. Thus, there is a critical need to identify virus and host mechanisms that regulate cytokine expression to allow for intervention strategies to control disease pathogenesis. In this report, we discuss the role of cytokines and chemokines in the response to RSV infection, and the potential role for suppressor of cytokine signaling (SOCS) proteins in regulating these responses.  相似文献   

18.
The problem of tuberculosis is emerging again with increase in the population of aged people and immunocompromised patients in Japan. It has been well documented that cell-mediated immunity play a central role in host resistance to infection with Mycobacterium tuberculosis. Many recent studies have provided evidences suggesting that the Th1-Th2 cytokine balance may determine the outcome of some diseases: predominant production of Th1 cytokines may prevent the occurrence of infectious diseases caused by intracellularly growing pathogens and Th2 cytokines may be involved in the exacerbation of allergic diseases. On the other hand, IL-12 plays an essential role in the differentiation of Th1 cells from naive T cells, and IL-18 potentiates this effect although it does not show such effect by itself. In previous investigations using gene-disrupted mice, the essential roles for IFN-gamma, IL-12 and IL-18 have been demonstrated. There are several host factors which determines the outcome of mycobacterial infection. Among them, steroid treatment and AIDS are important factors. In this lecture, I addressed the effect of these pathological conditions on Th1-Th2 cytokine balance and outcome of mycobacterial infection using murine models. In both conditions, the exacerbated infection was well correlated with the reduced production of IFN-gamma. Furthermore, I also talked about the relationship between other host factors and balance in the production of Th1 and Th2 cytokines. Using a murine model of fatal infection with M. tuberculosis, we demonstrated the therapeutic effect of Th1-type cytokines against this infection and suggested that immunotherapy with these cytokines may be clinically effective in the intractable infection. We tried a combined therapy with anti-tuberculous agents and IFN-gamma in intractable pulmonary tuberculosis caused by multidrug-resistant pathogen in a patient with insulin-dependent diabetes mellitus. Although no report showing the clinical use of IL-12 in infectious diseases has been seen, clinical trials already commenced for the therapy of malignant neoplastic diseases. It may not be in far future that this cytokine is clinically used for the treatment of infectious diseases. IL-18 has not yet been under the clinical trials.  相似文献   

19.
Experimental Leishmania major infection in mice: role of IL-10   总被引:1,自引:0,他引:1  
L. major infection of mice induces polarized Th1 and Th2 responses that are correlated with healing of the infection (Th1) or a fatal disease (Th2). The Th subset specific cytokines, IFNgamma and IL-4, themselves were shown to be important factors for the differentiation into the Th1 and Th2 pathways during infection. We studied the role of the Th2 cytokine IL-10 during leishmania infection: removal of endogenous IL-10 by anti-IL-10 treatment did not alter the Th2 cytokine pattern in non-healer mice nor did it modulate DTH reactivity, IgE production or fatal disease progression, but partially blocked the IFNgamma inhibiting effect of rIL-4 in healer mice. During chronic infection similar amounts of IL-10 were produced in both healer and non-healer mice. However, at early time-points during infection IL-10 production was significantly higher in the non-healer Th2 responder animals. IL-10 production in vitro caused significant inhibition of in vitro IFNgamma production. In conclusion IL-10, unlike IL-4 and IFNgamma, does not seem to play a readily detectable role in the Th subset differentiation during L. major infection. However, the high production of IL-10 early during infection in non-healer mice and inhibition of leishmania-specific IFNgamma production may contribute to drive the immune response towards a Th2 response.  相似文献   

20.
The problem of tuberculosis is emerging again with increase in the population of aged people and immunocompromised patients in Japan. It has been well documented that cell-mediated immunity play a central role in host resistance to infection with Mycobacterium tuberculosis. A decade years ago, Mosmann et al. found that helper T (Th) cells are divided into two subsets, Th1 and Th2, based on the cytokines which they produce. Th1 cells produce IFN-gamma, while Th2 cells secrete IL-4, IL-10 and IL-13. Many recent studies have provided evidences suggesting that the Th1-Th2 cytokine balance may determine the outcome of some diseases. For example, predominant production of Th1 cytokines may prevent the occurrence of infectious diseases caused by intracellularly growing pathogens and Th2 cytokines may be involved in the exacerbation of allergic diseases. On the other hand, IL-12 plays an essential role in the differentiation of Th1 cells from naive T cells, and IL-18 potentiates this effect although it does not show such effect by itself. In the present study, we examined the role for these two cytokines in host resistance to mycobacterial infection by using an animal model with either IL-12 or IL-18 gene-disrupted mice. The organ loads of this pathogen in lung, liver and spleen were significantly larger in these gene-disrupted mice than those in control mice. There are several host factors which determines the outcome of mycobacterial infection. Among them, steroid treatment and AIDS are important factors. In this study, we determined the effect of these pathological conditions on Th1-Th2 cytokine balance and outcome of mycobacterial infection using murine models. In both conditions, the exacerbated infection was well correlated with the reduced production of IFN-gamma. Furthermore, I also discussed about the relationship between other host factors and balance in the production of Th1 and Th2 cytokines.  相似文献   

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