scholarly journals Gene Transcription Profile in Mice Vaccinated with Ultraviolet-attenuated Cercariae of Schistosoma japonicum Reveals Molecules Contributing to Elevated IFN-γ Levels

2005 ◽  
Vol 37 (4) ◽  
pp. 254-264 ◽  
Author(s):  
Xiang Zhu ◽  
Zhao-Song Zhang ◽  
Min-Jun Ji ◽  
Hai-Wei Wu ◽  
Yong Wang ◽  
...  

AbstractVaccination with ultraviolet-attenuated cercariae of Schistosoma japonicum induced protective immunity against challenge infection in experimental animal models. Our preliminary study on the transcription levels of IFN-γ and IL-4 in splenic CD4+ T cells revealed that attenuated cercariae elicited predominantly a Th1 response in mice at the early stage, whereas normal cercariae stimulated primarily Independent responses. Further analysis on the gene profile of the skin-draining lymph nodes demonstrated that the levels of IFN-γ were significantly higher in vaccinated mice than those in infected mice at day 4, 7 and 14 post-vaccination or post-infection. However, for IL-12 and IL-4, the potent inducers of Th1 and Th2 responses, respectively, as well as IL-10, there were no differences over the course of the experiment between the infected and vaccinated mice. To explore the underlying factors that may potentially contribute to elevated IFN-γ in vaccinated mice, the mRNA profiles of the skin-draining lymph nodes at day 4 post-exposure were compared using oligonucleotide microarrays. Within the 847 probe sets with increased signal values, we focused on chemokines, cytokines and relevant receptors, which were validated by semi-quantitative RT-PCR. A comprehensive understanding of the immune mechanisms of attenuated cercariae-induced protection may contribute to developing efficient vaccination strategies against S. japonicum, especially during the early stage of infection.

2004 ◽  
Vol 72 (8) ◽  
pp. 4521-4527 ◽  
Author(s):  
Eduardo Fonseca Pinto ◽  
Roberta Olmo Pinheiro ◽  
Alice Rayol ◽  
Vicente Larraga ◽  
Bartira Rossi-Bergmann

ABSTRACT We have previously demonstrated that oral delivery of a disease-promoting particulated antigen of Leishmania amazonensis (LaAg) partially protects mice against cutaneous leishmaniasis. In the present work, we sought to optimize a mucosal vaccine by using the intranasal route for delivery of different antigen preparations, including (i) LaAg, (ii) soluble recombinant p36/LACK leishmanial antigen (LACK), and (iii) plasmid DNA encoding LACK (LACK DNA). BALB/c mice that received two intranasal doses of 10 μg of LaAg and were challenged 1 week postvaccination with L. amazonensis developed delayed but effective control of lesion growth. A diminished parasite burden was accompanied by enhancement of both gamma interferon (IFN-γ) and interleukin-10 levels in the lesion-draining lymph nodes. The vaccine efficacy improved with time. At 4 months postvaccination, when a strong parasite-specific TH1-type response was present in vivo, the infection was controlled for at least 5 months after challenge. In contrast to the particulated LaAg, soluble LACK (10 μg/dose) had no effect. Interestingly, LACK DNA (30 μg/dose), but not empty DNA, promoted rapid and durable protective immunity. Parasite growth was effectively controlled, and at 5 months after challenge LACK-reactive cells in both the mucosal and lesion-draining lymph nodes produced high levels of IFN-γ. These results demonstrate for the first time the feasibility of using the intranasal route for long-lived memory vaccination against cutaneous leishmaniasis with adjuvant-free crude antigens or DNA.


Parasitology ◽  
1998 ◽  
Vol 117 (4) ◽  
pp. 301-309 ◽  
Author(s):  
S. RIENGROJPITAK ◽  
S. ANDERSON ◽  
R. A. WILSON

A single exposure to radiation-attenuated cercariae of Schistosoma mansoni induces a high level of protective immunity in C57BL/6 mice, which is mediated by Th1 responses. Events in the skin and/or draining lymph nodes early after exposure are crucial for the induction of protection, and we have investigated the interactions of vaccinating parasites with host leucocytes in these 2 locations. We observed extensive lateral spreading of cercarial secretions along layers of the stratum corneum but not between keratinocytes. There was little direct contact with host leucocytes during the first 1–2 days when the parasites lay at the base of the epidermis, but cells accumulated in the underlying dermis. In contrast to normal parasites, attenuated larvae persisted in the dermis for >10 days, often surrounded by aggregates of macrophages/dendritic cells. Whilst cells bearing MHC II, CD11b or CD11c markers were present in the lymph nodes, particularly in the periphery and paracortical areas, no obvious redistribution was seen as a result of parasite residence there for 5–15 days. However, ultrastructural observations revealed numerous cells with macrophage/dendritic morphology in the vicinity of parasites, in some instances closely adherent to the tegument. The observations strongly suggest that the tegument is a potent source of the antigens which prime the immune system in the lymph nodes of vaccinated mice for a protective response.


Author(s):  
Mohammad Barati ◽  
Mehdi Mohebali ◽  
Ali Khamesipour ◽  
Fariborz Bahrami ◽  
Haiedeh Darabi ◽  
...  

Background: We aimed to investigate the potential effects of BCG and imiquimod on improvement of current experimental L. major vaccine against dogs in an endemic area of Zoonotic visceral leishmaniasis (ZVL) in Iran. Methods: During 2012 till 2014, seven mixedbreed shepherd dogs with no anti-Leishmania antibodies and no response to Leishmanin reagent were immunized with 2 doses of alum-precipitated autoclaved L. major (Alum-AML) while BCG and imiquimod (for skin pre-treatment) were used as adjuvants. The productions of a few characteristic cytokines of T-helper immune responses and the development of delayed-type hypersensitivity (DTH) of the immunized animals were then evaluated, up to 300 days. Blood samples were collected at 0, 30, 80 and 300 d post-vaccination and the concentrations of IFN-γ, IL10, IL-12 and TGF-β cytokines secreted from PBMCs at these time-points were quantified by ELISA. DTH was evaluated by Leishmanin skin test (LST). Results: Although a similar LST conversion was observed at all time-points, the cytokine measurement results indicated significantly higher levels of IFN-γ at day 80 and elevated levels of IL-10 at days 80 and 300, post-vaccination. Moreover, a significantly higher IFN-γ/IL-10 ratio was observed at day 30 post-vaccination compared to the other time-points. Conclusion: Although a Th1-like response could be observed at day 30 post-vaccination, the development of cytokine profiles was inclined toward mixed Th1 and Th2 responses at days 80 and 300 post-vaccination. This situation may indicate the requirement of an additional boosting by this Alum-AML formula, in order to induce long-lasting protection against ZVL.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mohammad Maarouf ◽  
Alyaa A. Abdlwahab

Cutaneous leishmaniasis in Syria is caused mainly by Leishmania tropica. It represents a serious health problem, which has aggravated further after the civil war in the country. Until now, there are no effective protective strategies, safe therapy, or efficacious vaccine to protect from this infection. DNA vaccines represent a promising approach for achieving protection against leishmaniasis. The L5 ribosomal protein plays fundamental roles in the assembly process of the ribosome subunits, so this study has chosen the ribosomal protein L5 gene to design a DNA vaccine against Leishmania tropica infection. After proving the existence of the ribosomal protein L5 gene in a Syrian strain of Leishmania tropica (LCED Syrian 01), it was sequenced and cloned into a pCI plasmid, and the designed DNA vaccine was administered to BALB/c mice. The protective response was evaluated by measuring lesion development in immunized BALB/c mice for 6 weeks after challenging mice with the parasite. RT-qPCR was used to quantify IL-12, IFN-γ, and IL-4 in draining lymph nodes (DLNs) of immunized mice. In the final week, the parasite burden was determined in footpad lesions and local draining lymph nodes (DLNs). This study demonstrated the presence and expression of the ribosomal protein L5 gene in the Syrian strain of Leishmania tropica promastigotes. The sequence of the ribosomal protein cDNA L5 gene was determined and published in Genbank. The gene size was 918 bp. Expression was also demonstrated at the level of cDNA. This study also demonstrated that vaccination with the ribosomal protein L5 gene induces TH1 response in immunized mice. This response prevents the partial development of a skin lesion of Leishmania.


Tumor Biology ◽  
2016 ◽  
Vol 37 (11) ◽  
pp. 14659-14666 ◽  
Author(s):  
Morteza Jafarinia ◽  
Fereshteh Mehdipour ◽  
Seyed Vahid Hosseini ◽  
Leila Ghahramani ◽  
Masood Hosseinzadeh ◽  
...  

1999 ◽  
Vol 67 (6) ◽  
pp. 2713-2719 ◽  
Author(s):  
Catherine Cêtre ◽  
Christine Pierrot ◽  
Cécile Cocude ◽  
Sophia Lafitte ◽  
André Capron ◽  
...  

ABSTRACT In contrast to most mouse strains, rats eliminate the primary schistosome burden around 4 weeks postinfection and subsequently develop protective immunity to reinfection. In rat schistosomiasis, we have shown predominant expression of a Th2-type cytokine response at the mRNA level after primary infection. In the present study, we showed a significant increase in interleukin-4 (IL-4) mRNA expression in inguinal lymph nodes early after a secondary infection. IL-5 mRNA expression showed a significant increase at days 2 and 4 postreinfection in the spleen and lymph nodes, respectively. We did not detect any gamma interferon (IFN-γ) mRNA after a challenge infection. Analysis of cytokine secretion by stimulated spleen cells after a primary infection showed predominant expression of IL-4 with maximum production on day 21, accompanied by production of IL-5 from day 11 to day 67. A significant increase in IFN-γ secretion was detected at day 21. Analysis of immunoglobulin G2b (IgG2b) and IgG2c (Th1-related isotypes) showed undetectable levels of IgG2b, but detectable levels of specific IgG2c antibodies were observed from day 42. The analysis of Th2-related isotypes showed high specific IgG1 and IgG2a antibody titers from day 29. After a secondary infection, only IL-4 and IL-5 secretion was sustained. This is supported by the increased production of Th2-related isotypes. These findings showed that S. mansoni infection can drive Th2 responses in rats in the absence of egg production which is required to induce a Th2 response in mice and are in favor of the role of Th2-type cytokines in protective immunity against reinfection.


2018 ◽  
Vol 97 (12) ◽  
pp. 1399-1405 ◽  
Author(s):  
J.L. Brown ◽  
L. Campbell ◽  
J. Malcolm ◽  
A. Adrados Planell ◽  
J.P. Butcher ◽  
...  

Innate lymphoid cells (ILCs) are a population of lymphocytes that act as the first line of immunologic defense at mucosal surfaces. The ILC family in the skin, lungs, and gastrointestinal tissues has been investigated, and there are reports of individual subsets of ILCs in the oral tissues. We sought to investigate the whole ILC population (group 1, 2, and 3 subsets) in the murine gingivae and the lymph nodes draining the oral cavity. We show that ILCs made up a greater proportion of the whole CD45+ lymphocyte population in the murine gingivae (0.356% ± 0.039%) as compared with the proportion of ILCs in the draining lymph nodes (0.158% ± 0.005%). Cytokine profiling of the ILC populations demonstrated different proportions of ILC subsets in the murine gingivae versus the regional lymph nodes. The majority of ILCs in the draining lymph nodes expressed IL-5, whereas there were equal proportions of IFN-γ- and IL-5 expressing ILCs in the oral mucosa. The percentage of IL-17+ ILCs was comparable between the murine gingivae and the oral draining lymph nodes. These data suggest an enrichment of ILCs in the murine gingivae, and these ILCs reflect a cytokine profile discrepant to that of the local draining lymph nodes. These studies indicate diversity and enrichment of ILCs at the oral mucosal surface. The function of ILCs in the oral cavity remains to be determined; here, we provide a premise of ILC populations that merits future consideration in investigations of mouse models and human tissues.


1999 ◽  
Vol 67 (2) ◽  
pp. 568-575 ◽  
Author(s):  
Yoshinari Tanabe ◽  
Huabao Xiong ◽  
Takamasa Nomura ◽  
Masaaki Arakawa ◽  
Masao Mitsuyama

ABSTRACT Only listeriolysin O (LLO)-producing strains of Listeria monocytogenes generate protective immunity in mice. Based on the findings that endogenous gamma interferon (IFN-γ) production was induced only by such strains and that purified LLO could induce IFN-γ from NK cells, we have postulated that LLO may play a pivotal role in the induction of Th1-type protective T cells, which are highly dependent on IFN-γ. In this study, mice were immunized with L. monocytogenes ATCC 15313, an LLO-nonproducing avirulent strain, along with LLO encapsulated in liposome (LLO-liposome). LLO-liposome was highly potent in the induction of various cytokines, including IFN-γ. Immunization of mice with either LLO-liposome or the viable strain ATCC 15313 alone did not induce protection against challenge infection. In contrast, the combination of LLO-nonproducing bacteria plus LLO-liposome induced a significant level of protective immunity mediated mainly by Th1-type cells capable of producing a large amount of IFN-γ in an antigen-specific manner. The protection afforded by the combination was not dependent on LLO-specific cytotoxic T cells. These results support the idea that the inability of an LLO-nonproducing avirulent strain or killed bacteria to induce the generation of protective T cells is due not to the lack of a central T-cell epitope(s) but to the lack of ability to induce the production of endogenous cytokine during the early stage of immunization; the results also suggest that an appropriate use of LLO at least in an animal model may be effective in the induction of antigen-specific Th1-dependent protective immunity to various kinds of intracellular parasitic bacteria.


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