scholarly journals TLR2 and TLR4 signaling pathways are required for recombinant Brucella abortus BCSP31-induced cytokine production, functional upregulation of mouse macrophages, and the Th1 immune response in vivo and in vitro

2014 ◽  
Vol 11 (5) ◽  
pp. 477-494 ◽  
Author(s):  
Jia-Yun Li ◽  
Yuan Liu ◽  
Xiao-Xue Gao ◽  
Xiang Gao ◽  
Hong Cai
2013 ◽  
Vol 81 (5) ◽  
pp. 1654-1662 ◽  
Author(s):  
Leonardo A. de Almeida ◽  
Gilson C. Macedo ◽  
Fábio A. V. Marinho ◽  
Marco T. R. Gomes ◽  
Patrícia P. Corsetti ◽  
...  

ABSTRACTBrucella abortusis recognized by several Toll-like receptor (TLR)-associated pathways triggering proinflammatory responses that affect both the nature and intensity of the immune response. Previously, we demonstrated thatB. abortus-mediated dendritic cell (DC) maturation and control of infection are dependent on the adaptor molecule MyD88. However, the involvement of all TLRs in response toB. abortusinfection is not completely understood. Therefore, we decided to evaluate the requirement for TLR6 in host resistance toB. abortus. Here, we demonstrated that TLR6 is an important component for triggering an innate immune response againstB. abortus. Anin vitroluciferase assay indicated that TLR6 cooperates with TLR2 to senseBrucellaand further activates NF-κB signaling. However,in vivoanalysis showed that TLR6, not TLR2, is required for the efficient control ofB. abortusinfection. Additionally,B. abortus-infected dendritic cells require TLR6 to induce tumor necrosis factor alpha (TNF-α) and interleukin-12 (IL-12). Furthermore, our findings demonstrated that the mitogen-activated protein kinase (MAPK) signaling pathway is impaired in TLR2, TLR6, and TLR2/6 knockout (KO) DCs when infected withB. abortus, which may account for the lower proinflammatory cytokine production observed in TLR6 KO mouse dendritic cells. In summary, the results presented here indicate that TLR6 is required to trigger innate immune responses againstB. abortusin vivoand is required for the full activation of DCs to induce robust proinflammatory cytokine production.


2006 ◽  
Vol 74 (5) ◽  
pp. 2734-2741 ◽  
Author(s):  
Deyan Luo ◽  
Bing Ni ◽  
Peng Li ◽  
Wei Shi ◽  
Songle Zhang ◽  
...  

ABSTRACT This study was designed to evaluate the immunogenicity and the protective efficacy of a divalent fusion DNA vaccine encoding both the Brucella abortus L7/L12 protein (ribosomal protein) and Omp16 protein (outer membrane lipoprotein), designated pcDNA3.1-L7/L12-Omp16. Intramuscular injection of this divalent DNA vaccine into BALB/c mice elicited markedly both humoral and cellular immune responses. The specific antibodies exhibited a dominance of immunoglobulin G2a (IgG2a) over IgG1. In addition, the dual-gene DNA vaccine elicited a strong T-cell proliferative response and induced a large amount of gamma interferon-producing T cells upon restimulation in vitro with recombinant fusion protein L7/L12-Omp16, suggesting the induction of a typical T-helper-1-dominated immune response in vivo. This divalent DNA vaccine could also induce a significant level of protection against challenge with the virulent strain B. abortus 544 in BALB/c mice. Furthermore, the protection level induced by the divalent DNA vaccine was significantly higher than that induced by the univalent DNA vaccines pcDNA3.1-L7/L12 or pcDNA3.1-Omp16. Taken together, the results of this study verify for the first time that the Omp16 gene can be a candidate target for a DNA vaccine against brucellosis. Additionally, a divalent genetic vaccine based on the L7/L12 and Omp16 genes can elicit a stronger cellular immune response and better immunoprotection than the relevant univalent vaccines can.


1999 ◽  
Vol 67 (8) ◽  
pp. 3786-3792 ◽  
Author(s):  
Joanna Kirman ◽  
Kathy McCoy ◽  
Sarah Hook ◽  
Melanie Prout ◽  
Brett Delahunt ◽  
...  

ABSTRACT The murine immune response to a pulmonary mycobacterial infection is slow to develop, allowing bacterial numbers to increase in the lung for several weeks after infection. We sought to enhance the protective immune response induced during Mycobacterium bovis BCG infection by administering an antibody that blocks the interaction of CTLA-4 with its ligands, CD80 and CD86. We found that injection of anti-CTLA-4 monoclonal antibody (MAb) greatly enhanced and accelerated the immune response, as measured by increased cellularity of the draining mediastinal lymph nodes, and enhanced antigen-inducible proliferation and gamma interferon production by mediastinal lymphocytes in vitro. However, despite the apparently enhanced immune response in the mediastinal lymph node following treatment with anti-CTLA-4 MAb, there was no improvement in clearance of mycobacteria in the lungs, liver, or spleen. Examination of the primary site of infection, the lung, revealed that CTLA-4 blockade had no effect on the number or function of lymphocytes infiltrating the infected lung tissue. Taken together, these data suggest that in vivo CTLA-4 blockade enhances mycobacterial-infection-induced lymphocyte expansion and effector cell cytokine production in the draining lymph node but does not alter the number or function of lymphocytes at the primary site of infection and therefore does not lead to enhanced clearance of the infection.


1994 ◽  
Vol 22 (03n04) ◽  
pp. 255-266 ◽  
Author(s):  
Rui Jin ◽  
Ling Ling Wan ◽  
Toshimi Mitsuishi ◽  
Shinobu Sato ◽  
Yuki Akuzawa ◽  
...  

Shi-Ka-Ron is a prescription composed of 8 crude extracts of Chinese herbs. It reduces suppression of cytokine production by peritoneal macrophages in mice Immunocompromised by the anti-tumor agent, cyclophosphamide (CY), in vivo. Although it dose not increase IL-1 production in vitro, it enhances TNF production. We found that Ginseng radix, Lithospermi radix, Astragli radix and Glycyrrhizae radix somewhat reduced suppression of cytokine production in CY treated macrophages. Especially, Glycyrrhizae radix shows an active immune response both in vivo and in vitro. Our results suggested that the mechanism underlying immunomodulation of Shi-Ka-Ron is closely related to cytokine production: each herb stimulating macrophages.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yang Tao ◽  
Deqing Wang ◽  
Yuanliang Hu ◽  
Yee Huang ◽  
Yun Yu ◽  
...  

The aim of this study was to investigate and assess the effects of propolis flavonoids liposome imposed on the immune system by comparing it to propolis flavonoids and blank liposome.In vitro, the effects of the above drugs on macrophages were assessed by measuring the phagocytic function and cytokine production.In vivo, the immunological adjuvant activity of propolis flavonoids liposome was compared with those of propolis flavonoids and blank liposome. The results showed thatin vitropropolis flavonoids liposome can significantly enhance the phagocytic function of macrophages and the release of IL-1β, IL-6, and IFN-γ. In addition, subcutaneous administration of propolis flavonoids liposome with ovalbumin to mice could effectively activate the cellular and humoral immune response, including inducing higher level concentrations of IgG, IL-4, and IFN-γin serum and the proliferation rates of splenic lymphocytes. These findings provided valuable information regarding the immune modulatory function of propolis flavonoids liposome and indicated the possibility of use of propolis flavonoids liposome as a potential adjuvant.


2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Cecilia Gomes Barbosa ◽  
Tamires Marielem Carvalho Costa ◽  
Chamberttan Souza Desidério ◽  
Paula Tatiana Mutão Ferreira ◽  
Mariana de Oliveira Silva ◽  
...  

Dendritic cells (DCs) are a type of antigen-presenting cells that play an important role in the immune response against Trypanosoma cruzi, the causative agent of Chagas disease. In vitro and in vivo studies have shown that the modulation of these cells by this parasite can directly affect the innate and acquired immune response of the host in order to facilitate its biological cycle and the spreading of the species. Many studies show the mechanisms by which T. cruzi modulates DCs, but the interaction of these cells with the Mexican strains of T. cruzi such as Ninoa and INC5 has not yet been properly investigated. Here, we evaluated whether Ninoa and INC5 strains evaded the immunity of their hosts by modulating the biology and function of murine DCs. The CL-Brener strain was used as the reference strain. Herein, it was demonstrated that Ninoa was more infective toward bone marrow-derived dendritic cells (BMDCs) than INC5 and CL-Brener strains in both BMDCs of BALB/c and C57BL/6 mice. Mexican strains of T. cruzi induced different cytokine patterns. In BMDCs obtained from BALB/c mice, Ninoa strain led to the reduction in IL-6 and increased IL-10 production, while in C57BL/6 mice Ninoa strain considerably increased the productions of TNF-α and IL-10. Also, Ninoa and INC5 differentially modulated BMDC expressions of MHC-II, TLR2, and TLR4 in both BALB/c and C57BL/6 mice compared to Brazilian strain CL-Brener. These results indicate that T. cruzi Mexican strains differentially infect and modulate MHC-II, toll-like receptors, and cytokine production in DCs obtained from C57BL/6 and BALB/c mice, suggesting that these strains have developed particular modulatory strategies to disrupt DCs and, consequently, the host immune responses.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Shikui Xu ◽  
Aixue Zuo ◽  
Zengjun Guo ◽  
Chunping Wan

The present study was designed to assess the antiarthritic potential of ECF in collagen-induced arthritis (CIA) and explore its underlying mechanism. Methods. In vitro, lymphocyte proliferation assay was measured by CCK-8 kit. In vivo, the therapeutic potential of ECF on CIA was investigated; surface marker, Treg cell, and intracellular cytokines (IL-17A and IFN-γ) were detected by flow cytometry. Th1 cell differentiation assay was performed, and mRNA expression in interferon-γ-related signaling was examined by q-PCR analysis. Results. In vitro, ECF markedly inhibited the proliferation of splenocytes in response to ConA and anti-CD3. In vivo, ECF treatment reduced the severity of CIA, inhibited IFN-γ and IL-6 secretion, and decreased the proportion of CD11b+Gr-1+ splenic neutrophil. Meanwhile, ECF treatment significantly inhibited the IFN-γ expression in CD4+T cell without obviously influencing the development of Th17 cells and T regulatory cells. In vitro, ECF suppressed the differentiation of naive CD4+ T cells into Th1. Furthermore, ECF intensely blocked the transcriptional expression in interferon-γ-related signaling, including IFN-γ, T-bet, STAT1, and STAT4. Conclusion. Our results indicated that ECF exerted antiarthritic potential in collagen-induced arthritis by suppressing Th1 immune response and interferon-γ-related signaling.


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