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The Effects Of Trichinella Spiralis Infection On The Differentiation And Maturation Of Dendritic Cells And The Immunological Mechanisms

Posted on:2016-04-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:J JiangFull Text:PDF
GTID:1223330503468344Subject:Prevention of Veterinary Medicine
Abstract/Summary:PDF Full Text Request
Trichinella spiralis are the smallest nematode parasite of humans, have an unusual lifecycle, and are one of the most widespread and clinically important parasites in the world.The disease has seriously affected public health and food safety, and also caused the impact to the animal husbandry.Dendritic cells(DC) belong to professional antigen-presenting cells(Antigen presenting Cells, APC), is the the first encounter of a class of cells after the invasion of pathogenic microorganisms in the host organism,they can uptake, processing and presentation of antigens in acquired immune response process.During evolution, helminth parasites have influenced the vertebrate immune system resulting in distinctive features of the infected host ’ s immune response. Based on the continuous molecular dialog between the pathogen and the host, helminths have developed different evasion and suppression mechanisms enabling establishment of infection with the lowest possible damage to the host. Trichinella spiralis establish a long-term infection in the skeletal muscle of the host, depending on the life of the host, they even always exist until the death of the host, and still has infectivity a few months to several years after the death of the host.In this experiment, we use Trichinella antigen to stimulate mouse neck lymphocytes in vitro, detecting DC differentiation and maturation. The results showed that the DCs treated by the ES, analyzed by flow cytometry,the CD11 c positive rate is more than 70%, the costimulatory factorsof CD40 + and B7(CD80+, CD86+) in the expression levels have increased, and the difference was significant, indicated that ES stimulation DC development is not fully mature state, changing the DC function. In the T lymphocyte proliferative response experiments, DC as stimulator cells, when mature DCs was inhibited, T cell proliferation levels also decreased, thereby inhibiting the T cell-mediated immune response, immune evasion and make Trichinella in long-term survival of the host body, and the body is in the chronic infection phase. The IL-10 secretion levels of DCs which were treated by the Trichinella spiralis ES antigen have significantly increased, and the levels of IL-12 was reduced, indicating that Trichinella infection caused the broken balance of host Th1 / Th2, mainly to induce Th2 differentiation.We also analyzed by flow cytometry in vivo to study the effect by Trichinella infection on the differentiation of mouse DC, after three weeks of Trichinella infection, compared with the PBS group, in the Trichinella infection group, in MLN spleen and lymph node the proportion of the DC subsets, CD11c+CD11b+CD8a-, CD11c+ B220+CD8a+and CD11c+B220+CD8a- have be increased(P<0.05), indicating that Trichinella infection promote the differentiation of these DCs cell subsets.After Trichinella infection, mice spleen and lymph nodes MLN local mucosal surface of DC maturation markers CD40 +, MHC-II and B7 costimulatory factor(CD80 +, CD86 +) expression levels increased(P <0.05), but three weeks after infection, the activation level of Trichinella infection MLN spleen and lymph nodes in the local mucosal surface DC maturation markers(MHC-II and CD86+) was decreased,indicating that Trichinella infection in chronic phase DC antigen-presenting function was inhibited. The expression levels of MyD88 in different infection days was consistent to the life cycle. The expression of MyD88 wassignificantly inhibited by RNA interference, thus blocking the TLR signal transduction.
Keywords/Search Tags:Trichinella spiralis, dendritic cell, differentiation and Maturation, immunological mechanism
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