284. Leukocyte trafficking in the ovary of mice immunised with recombinant murine cyclomegalovirus expressing murine zona pellucida 3

2005 ◽  
Vol 17 (9) ◽  
pp. 119
Author(s):  
S. O'Leary ◽  
M. L. Lloyd ◽  
G. R. Shellam ◽  
S. Maddocks

Inoculation of female BALB/c mice with recombinant murine cytomegalovirus encoding murine zona pellucida antigen (MCMV-ZP3) confers infertility characterised by depletion in ovarian tertiary follicles by day 21 post inoculation followed by a progressive depletion in primordial follicles.1 Cell mediated immune responses begin as early as day 10 post immunisation with MCMV-ZP32 with the recruitment of leukocytes before serum antibody can be clearly detected in mice. The physiological mechanisms leading to infertility in inoculated mice are being progressively delineated with the role of leukocyte subsets implicated in early pathological changes in ovarian architecture. The aim of this study was to investigate the effect of MCMV-ZP3 infection on leukocytes including T cells recruited into the ovary following infection with recombinant virus. Fifteen BALB/c female mice were randomly allocated into three groups of five animals at 6 weeks of age. Group one received an injection of PBS, group two and three received intraperitoneal inoculations of 2 × 104 pfu of MCMV and MCMV-ZP3 respectively. Ovaries were retrieved at day 10, 21 and 35 post inoculation and one ovary from each mouse was sectioned for immunohistochemical analysis of resident leukocytes using mAb CD45 reactive with all leukocyte lineages and mAb for CD4 and CD8 positive T cells. MCMV-ZP3 inoculation increased the abundance of ovarian leukocytes including CD4 and CD8 positive T cells for all time points post immunisation except for CD8 positive T cells 21 days post infection (Table 1). These results suggest that leukocytes, including T cells, are involved in causing early changes in the ovary post infection with MCMV-ZP3 that lead to the depletion of existing ovarian follicles leading to life long infertility in mice. Further experiments are underway to investigate the role of antibody and changes in leukocyte populations in the ovary as the course of infection with recombinant virus progresses. This study is funded by the Cooperative Research Centre for Pest Animal Control. (1)Lloyd ML, et al. (2003). Biol. Reprod. 68, 2024–32.(2)O’Leary S, et al. (2004). Reprod. Fertil. Devel. 16(Supplement), 77.

2004 ◽  
Vol 16 (9) ◽  
pp. 223
Author(s):  
S. O'Leary ◽  
M. L. Lloyd ◽  
G. R. Shellam ◽  
S. Maddocks

Immunocontraception is a promising biological control for wild mice in Australia, having the potential to reduce the socioeconomic cost of plagues with minimal environmental impact. Inoculation of BALB/c mice with recombinant murine cytomegalovirus encoding murine zona pellucida antigen (mCMV-ZP3) confers total infertility characterised by depletion in ovarian tertiary follicles by Day 21 post inoculation followed by a progressive depletion in primordial follicles (1). The mechanisms underlying ovarian pathology are largely unknown but are likely to involve antibody mediated and cell mediated immune responses. The immune pathology may also be facilitated by acute responses involving antibody binding to ZP in growing follicles resulting in recruitment of inflammatory cells and oocyte destruction. The aim of this study was to investigate the effect of mCMV–ZP3 infection on leukocyte infiltration and expression of oocyte-derived signalling molecules in ovarian tissue. Fifteen BALB/c female mice were randomly allocated into three groups of 5 animals. Group one received an injection of PBS, group two and three received intraperitoneal inoculations of 2�×�104�p.f.u. of mCMV and mCMV-ZP3 respectively. Ovaries were retrieved at Day 7 post inoculation and one ovary from each mouse was sectioned for immunohistochemical analysis of resident leukocytes using mAb CD45 reactive with all leukocyte lineages. The other ovary was processed for real time quantitative RT-PCR analysis of growth and differentiation factor 9 (GDF-9) and connexin 43 (Cx43) expression. mCMV-ZP3 inoculation increased the abundance of ovarian leukocytes (P�=�0.08), significantly increased expression of Cx43 mRNA (p<0.05), but did not alter GDF-9 mRNA expression. These results suggest that changes in expression of ovarian regulators due to ZP3 immunisation begins early after recombinant MCMV infection in mice, and implicates leukocyte infiltration in the mechanism leading to permanent ovarian failure. Further experiments are underway to investigate the dynamics of leukocyte trafficking and expression of oocyte-derived signals as the course of infection progresses. This study is funded by the Cooperative Research Centre for Pest Animal Control. (1) Lloyd, M. L., et al. (2003). Biology of Reproduction 68(6): 2024-32.


2004 ◽  
Vol 16 (9) ◽  
pp. 222
Author(s):  
M. L. Lloyd ◽  
J. M. Papadimitriou ◽  
S. O'Leary ◽  
M. A. Lawson ◽  
G. R. Shellam

A recombinant mouse virus, murine cytomegalovirus, that has been engineered to encode the fertility antigen murine zona pellucida 3 (mZP3), is being developed for fertility control in mice. A single inoculation of the recombinant virus induces complete infertility in female BALB/c mice which persists for the breeding life of the animal. The extent of this autoimmune response was unexpected especially as the incorporation of mZP3 appears to have immunologically attenuated the growth of the recombinant virus. The histological features of the infection are an initial depletion in tertiary follicles by 21 days post inoculation followed by a progressive depletion of primordial follicles, leading to an almost complete absence of follicles by 150 days post-infection. High titre, long lasting, zona pellucida-specific antibody is present in infertile BALB/c mice although infertility has not been linked with either a critical titre or a dominant immunoglobulin isotype. However, our evidence suggests that anti-ZP3 antibody plays a primary role in infertility since antibodies are detected in vivo bound to the zona pellucida of ovaries from recombinant virus-infected mice, and passively transferred antibody from infected animals induces infertility in the absence of recombinant virus. In addition, an experiment in which immunoglobulin-deficient mice remained fertile after inoculation with the recombinant virus indicates that antibody is crucial for the immunocontraceptive effect to occur. Other immune mechanisms are also being explored.


2007 ◽  
Vol 178 (8) ◽  
pp. 5209-5216 ◽  
Author(s):  
Kazuo Tanaka ◽  
Sadaaki Sawamura ◽  
Tadayuki Satoh ◽  
Kiyoshi Kobayashi ◽  
Satoshi Noda

2021 ◽  
Author(s):  
Wajiha Gohir ◽  
Lisa McTaggart ◽  
Julianne V. Kus ◽  
Tony Mazzulli ◽  
Deepali Kumar ◽  
...  

Background: We aimed to determine whether T cell-specific STAT3 deletion influences the immune response to Aspergillus in the immunosuppressed context in CD4Stat3-/- mice. Methods: Immunosuppressed and non-immunosuppressed CD4Stat3-/- mice and littermate Stat3fl/fl mice infected with Aspergillus fumigatus in an aerosol chamber and mice weight, activity, appearance and respiratory rate was monitored daily for 21 days to evaluate their survival. Aspergillus infection was confirmed by lung fungal culture counts, histology, and galactomannan test. Cytokines were measured 3 days post infection in BAL and serum. Results: Immunosuppressed CD4Stat3-/- mice began succumbing to infection by day 4, and by day 7, only 30% of mice survived. Immunosuppressed Stat3flox/flox (fl/fl) mice started to succumb to the disease on day 5, and 40% of mice remained by day 7. The non-immunosuppressed control Stat3fl/fl and CD4Stat3-/- mice maintained their weight over study period, without any evidence of infection by A. fumigatus by histology. In the BAL, TNFα, IL-6, IFNγ, IL-17A, and IL-22 levels were elevated in Stat3fl/fl immunosuppressed mice compared to immunosuppressed CD4Stat3-/- mice three days post-infection. Conclusion: STAT3 in CD4+ T cells modulates the production of cytokines in the IL-17 pathway in immunosuppressed mice. However, it has no meaningful effect on the clearance of Aspergillus nor the concomitant increase in susceptibility to Aspergillus infection.


2004 ◽  
Vol 26 (1) ◽  
pp. 23 ◽  
Author(s):  
K Higginbottom ◽  
CL Northrope ◽  
DB Croft ◽  
B Hill ◽  
E Fredline

Generally absent from the debate on the management of kangaroos (Macropodoidea) is discussion of their role in tourism. This paper examines the role that kangaroos play in Australian tourism, synthesising the findings of four related projects undertaken recently by the Cooperative Research Centre for Sustainable Tourism. It investigates the role of kangaroos in tourism marketing imagery, international tourist demand and existing tourism enterprises, and examines opportunities for future development of tourism involving kangaroos. In order to assess these aspects, experimental studies, interviews, visitor surveys, content analysis of advertising material, postal surveys of wildlife professionals and site visits were conducted. The kangaroo was found to be one of the world?s best-recognised tourism icons and to generate positive responses among Americans; yet it is apparently under-utilised in overseas travel brochures designed to attract international tourists to Australia. The use of kangaroos in tourism is already widespread, with over 190 tourism enterprises including kangaroo viewing, and with the kangaroo featuring in organised wildlife tourism more frequently than any other type of animal. However kangaroos are generally just one component of a broader tourism experience. While 18.4% of international visitors are motivated to visit Australia partly because of its native animals, there are very few who would not come otherwise. Kangaroos and koalas (Phascolarctos cinereus) are by far the most popular animals with international visitors. Most visitors who wished to do so, succeeded in seeing kangaroos during their visit, and most expressed high levels of satisfaction with their wildlife experiences. The most satisfying kangaroo viewing experiences are likely to involve the relatively large, social species of open habitats. However areas where these species are most likely to be abundant mostly score poorly in terms of feasibility of tourism. Tourism is one significant management option for Australia?s kangaroos, and its potential deserves further investigation.


2009 ◽  
pp. 1-8
Author(s):  
Jing-Lei Qu ◽  
Xiu-Juan Qu ◽  
Ming-Fang Zhao ◽  
Yue-E Teng ◽  
Ye Zhang ◽  
...  

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