Vaccination evokes gender-dependent protection against tularemia infection in C57BL/6Tac mice

Francisella tularensis (Ft) is a Category A biothreat agent for which there currently is no FDA-approved vaccine. Thus, there is a substantial effort underway to develop an effective tularemia vaccine. While it is well established that gender can significantly impact susceptibility to primary infection, the impact of gender on vaccine efficacy is not well established. Thus, development of a successful vaccine against tularemia will require an understanding of the impact gender has on vaccine-induced protection against this organism. In this study, a role for gender in vaccine-induced protection following Ft challenge is identified for the first time. In the present study, mucosal vaccination with inactivated Ft (iFt) LVS elicited gender-based protection in C57BL/6Tac mice against respiratory challenge with Ft LVS. Specifically, vaccinated male mice were more susceptible to subsequent Ft LVS challenge. This increased susceptibility in male mice correlated with increased bacterial burden, increased tissue inflammation, and increased proinflammatory cytokine production late in post-challenge infection. In contrast, improved survival of iFt-vaccinated female mice correlated with reduced bacterial burden and enhanced levels of Ft-specific Abs in serum and broncho-alveolar lavage (BAL) fluid post-challenge. Furthermore, vaccination with a live attenuated vaccine consisting of an Ft LVS superoxide dismutase (SodB) mutant, which has proven efficacious against the highly virulent Ft SchuS4 strain, demonstrated similar gender bias in protection post-Ft SchuS4 challenge. Of particular significance is the fact that these are the first studies to demonstrate that gender differences impact disease outcome in the case of lethal respiratory tularemia following mucosal vaccination. In addition, these studies further emphasize the fact that gender differences must be a serious consideration in any future tularemia vaccine development studies.     

Behavioral conditioning of endotoxin-induced plasma iron alterations

The cascade of physiologic mechanisms in response to infection, the acute-phase response, is recognized as playing a major role in host defence. One such response is the hypoferremia that is consistently reported to occur during bacterial infection. This study aimed to determine whether the alterations in plasma iron were conditionable using the conditioned taste aversion (CTA) paradigm. The regime involved the pairing of a novel-tasting saccharin solution with bacterial endotoxin. Seven days after the initial pairing of these stimuli (the test day), the saccharin solution was represented. Animals exposed to this condition displayed a significant reduction in the level of plasma iron. Animals treated with an intraperitoneal dose of 400 μg/Kg lipopolysaccharide (LPS) displayed lower conditioned iron levels than rats infused with 100 μg/Kg LPS; however, this difference was not significant. These results showed that in addition to other acute-phase responses (fever and anorexia), plasma iron alterations are able to be manipulated through behavioral manipulations.     

Clearance of Theiler's virus infection depends on the ability to generate a CD8+ T cell response against a single immunodominant viral peptide

Theiler's murine encephalomyelitis virus (TMEV) induces a chronic demyelinating disease in the central nervous system of susceptible mice. Resistance to persistent TMEV infection maps to he D locus of the major histocompatibility complex suggesting a prominent role of antiviral CTL in the protective immune response. Introduction of the D(b) gene into the FVB strain confers resistance to this otherwise susceptible mouse line. Infection of the FVB/D(b) mouse with TMEV provides a model where antiviral resistance is determined by a response elicited by a single class I molecule. Resistant mice of the H-2(b) haplotype mount a vigorous H-2D(b)-restricted immunodominant response to the VP2 capsid protein. To investigate the extent of the contribution of the immunodominant T cell population in resistance to TMEV, FVB/D(b) mice were depleted of VP2-specific CD8(+) T cells by peptide treatment prior to virus infection. Peptide-treated mice were not able to clear the virus and developed extensive demyelination. These findings demonstrate that the D(b)-restricted CD8(+) T cells specific for a single viral peptide can confer resistance to TMEV infection. Our ability to manipulate this cellular response provides a model for investigating the mechanisms mediating protection against virus infection by CD8(+) T cells.     

Varied biologic functions of c-reactive protein

Our investigations of human C-reactive protein (CRP) and CRP transgenic mice have produced novel data that firmly establish this protein as an important host defense molecule. For example, we have learned that depending on the disease model, the beneficial effect of CRP can be direct, depend on the protein's ability to engage complement and Fcγreceptors, or rely on its ability to bridge innate and adaptive immunity. In addition, the degree of protection correlates with acute phase expression, but more important, also with the amount of CRP expressed constitutively. Furthermore, differences in baseline levels of CRP among healthy individuals and among patients can be attributed to a CRP gene polymorphism. In this article, we discuss these and other observations we have made during the last 5 yr and summarize our ongoing studies and future plans related to CRP biology.     

用宿主防御指数辅助诊断中医虚证和不同辩证虚证的探讨

以中医学“虚证”及不同辩证虚证为研究对象，以宿主防御指数为研究总指标，开展了营养学和免疫学的多指标观察，并借助于医学统计学的理论和方法，尝试对中医学“虚证”的诊断。结果显示；虚证患者与正常人相比营养条件差，免疫功能氏下，主要表现为细胞免疫功能低下和免疫调节紊乱，补体主要成分降低，将这些评价指标代入计算机进行逐步判断分析，得出可以判别正常人，气阳虚患者，血阴虚患者的方程式，方程式判别能力Ｆ＝３（Ｐ〈     

无锡市肾综合症出血热宿主动物调查初报

对无锡市肾综合症出血热宿主动物调查结果表明:鼠类携带HFRS病毒阳性率5.77％。检出带病毒鼠4种,即小家鼠、黄胸鼠、褐家鼠、黑线姬鼠,其带病毒率分别为8.82％(3/34)、1.64％(1/61)、6.67％(2/30)、9.68％(3/31)。另外,经统计学分析,郊区带病毒鼠阳性明显高于市区(P<0.01)。加强灭鼠,严格控制疫区鼠密度是降低人群肾综合症出血热发病率的关键。     

Impact of a preceding striatal excitotoxic lesion and treatment with ciliary neurotrophic factor on striatal graft survival

The survival of grafted embryonic striatal tissue, dissected from the lateral ganglionic eminence, depends on the status of the host striatum. We found significantly larger volumes of surviving graft tissue and of striatal-like tissue (P-zone) within the graft, when the host striatum had been subjected to an excitotoxic lesion prior to transplantation surgery. Concomitantly the numbers of surviving grafted cells, assessed in both cresyl violet-stained sections and in sections stained with an immunohistochemical marker for striatal neurons, increased as compared to when graft tissue was placed in an intact unlesioned striatum. Finally, we examined the impact of treatment of the donor tissue with ciliary neurotrophic factor (CNTF) on graft survival. CNTF has previously been shown to protect striatal neurons against excitotoxic insults both in vitro and in vivo, but it did not improve striatal graft survival when added to the cell suspension prior to implantation.     

沂蒙山区1997～2003年肾综合征出血热监测结果分析

目的探讨肾综合征出血热（HFRS）在当地流行的特征和规律。方法统计分析沂蒙山区1997～2003年HFRS疫情资料。人群血清流行病学调查，HFRS疫苗接种效果观察。宿主动物带毒率调查采用荧光抗体实验（IFAT）方法，宿主动物密度调查采用夹夜法。结果1997～2003年全市累计报告HFRS病例32792例，年平均发病率为47．71／10万，男、女比例1．79：1（21051／11741），病例中农民占87．20％。健康人群HFRS抗体阳性率为1．85％。室内鼠密度平均为3．87％，野外平均为3．84％。鼠带毒率室内平均为5．05％，野外平均3．86％。HFRS临床诊断符合率平均85．26％。HFRS疫苗接种近期保护率为100％。结论当地HFRS的流行呈双峰型，疫区类型为家鼠型为主的混合型，HFRS疫苗接种近期预防效果肯定。     

山东省恙螨区系研究

目的　调查山东省恙螨的种类分布。方法　现场捕获鼠类及其他野生动物 ,采集体外恙螨 ,结合历次山东省恙螨调查研究文献收集种类资料。结果　已知山东省恙螨 3亚科 9属 2 4种 ,占中国已知恙螨 (4 5 3种 )的 5 .3 0 %。结论　基本摸清了山东省主要地区恙螨的种类区系分布 ,为深入开展恙虫病防治研究提供了依据。     

Invasive rabbits host immature Ixodes ticks at the urban-forest interface

Introduced wildlife may be important alternative hosts for generalist ticks that cause health issues for humans and companion animals in urban areas, but to date are rarely considered as part of the tick-host community compared to native wildlife. In Australia, European rabbits, Oryctolagus cuniculus, are a widespread and abundant invasive species common to a range of human-modified ecosystems. To understand the potential role of rabbits in the life cycle of Australian ticks, we investigated the seasonal abundance of all tick life stages (larva, nymph, and adult) on rabbits collected from pest control programs in two urban forest remnants in Sydney, Australia. We also recorded whether larvae, nymphs, and adults were attached to the head, body, or limbs of rabbits to reveal patterns of tick attachment. Of the 2426 Ixodes ticks collected from 42 rabbits, larvae were by far the most abundant life stage (2360), peaking in abundance in autumn, while small numbers of nymphs (62) and adults (4) were present in winter and summer respectively. Larvae were found all over the body, whereas adults and nymphs were predominantly attached to the head, suggesting that the mature life stages use the host landscape differently, or that adults or nymphs may be groomed off the body. The most abundant tick species, as determined by morphology and DNA sequencing, was Ixodes holocyclus, a generalist tick responsible for significant human and companion animal health concerns in Australia. Our findings highlight the importance of understanding the role of introduced wildlife in tick dynamics particularly in novel ecosystems where non-native hosts may be more abundant than native hosts.