Molecular battle between host and bacterium: recognition in innate immunity

During infection, our innate immune system is the first line of defense and has evolved to clear invading bacteria immediately. To do so, recognition is the key element. However, how does the innate immune system distinguish self from nonself, and how does it recognize all bacteria (estimated to be far over a million species)? The answer lies in the recognition of evolutionary conserved structures. In this review, we approach this phenomenon from the bacterial perspective. What are the evolutionary conserved structures in bacteria, and what strategies are there in the human innate immune system to sense these structures? We illustrate most examples both at the functional as well as at the molecular level. Furthermore, we highlight how pathogenic bacteria can evade this recognition to survive better in the human host which in turn can result in life‐threatening diseases. Copyright © 2011 John Wiley & Sons, Ltd.     

Identification and characterization of small RNAs involved in RNA silencing

Double-stranded RNA (dsRNA) is a potent trigger of sequence-specific gene silencing mechanisms known as RNA silencing or RNA interference. The recognition of the target sequences is mediated by ribonucleoprotein complexes that contain 21- to 28-nucleotide (nt) guide RNAs derived from processing of the trigger dsRNA. Here, we review the experimental and bioinformatic approaches that were used to identify and characterize these small RNAs isolated from cells and tissues. The identification and characterization of small RNAs and their expression patterns is important for elucidating gene regulatory networks.     

MicroRNAs as mediators of insect host–pathogen interactions and immunity

Insects are the most successful group of animals on earth, owing this partly to their very effective immune responses to microbial invasion. These responses mainly include cellular and humoral responses as well as RNA interference (RNAi). Small non-coding RNAs (snRNAs) produced through RNAi are important molecules in the regulation of gene expression in almost all living organisms; contributing to important processes such as development, differentiation, immunity as well as host–microorganism interactions. The main snRNAs produced by the RNAi response include short interfering RNAs, microRNAs and piwi-interacting RNAs. In addition to the host snRNAs, some microorganisms encode snRNAs that affect the dynamics of host–pathogen interactions. In this review, we will discuss the latest developments in regards to the role of microRNA in insect host–pathogen interactions and provide some insights into this rapidly developing area of research.     

Genetics-squared: combining host and pathogen genetics in the analysis of innate immunity and bacterial virulence

The interaction of bacterial pathogens with their hosts’ innate immune systems can be extremely complex and is often difficult to disentangle experimentally. Using mouse models of bacterial infections, several laboratories have successfully applied genetic approaches to identify novel host genes required for innate immune defense. In addition, a variety of creative bacterial genetic schemes have been developed to identify key bacterial genes involved in triggering or evading host immunity. In cases where both the host and pathogen are amenable to genetic manipulation, a combination of host and pathogen genetic approaches can be used. Focusing on bacterial infections of mice, this review summarizes the benefits and limitations of applying genetic analysis to the study of host–pathogen interactions. In particular, we consider how prokaryotic and eukaryotic genetic strategies can be combined, or “squared,” to yield new insights in host–pathogen biology.     

An analysis of the coexistence of two host species with a shared pathogen

Population dynamics of two-host species under direct transmission of an infectious disease or a pathogen is studied based on the Holt–Pickering mathematical model, which accounts for the influence of the pathogen on the population of the two-host species. Through rigorous analysis and a numerical scheme of study, circumstances are specified under which the shared pathogen leads to the coexistence of the two-host species in either a persistent or periodic form. This study shows the importance of intrinsic growth rates or the differences between birth rates and death rates of the two host susceptibles in controlling these circumstances. It is also demonstrated that the periodicity may arise when the positive intrinsic growth rates are very small, but the periodicity is very weak which may not be observed in an empirical investigation.      

RNA interference and its application in bone-related diseases

RNA interference (RNAi) is the most exciting insight in biology in past decades, which provided new perspectives into the genome-wide surveys of gene function by targeted degradation of mRNA with the introduction of small interfering RNAs (siRNAs) or small hairpin RNAs (shRNAs) in a large variety of organisms, and turned out to be a more efficient and convenient method compared with the traditional knockout pathway. What's more, as the enhancement of its stability and improvement of its delivery vehicles, RNAi is bound to be a practical tool in determine gene function first in vitro and then in vivo. In this paper, we will focus on the recent achievements of RNAi and also depict the development of RNAi as a potentially powerful tool in studying bone-related diseases.     

Effects of host heterogeneity on pathogen diversity and evolution

Phenotypic variation is common in most pathogens, yet the mechanisms that maintain this diversity are still poorly understood. We asked whether continuous host variation in susceptibility helps maintain phenotypic variation, using experiments conducted with a baculovirus that infects gypsy moth (Lymantria dispar) larvae. We found that an empirically observed tradeoff between mean transmission rate and variation in transmission, which results from host heterogeneity, promotes long‐term coexistence of two pathogen types in simulations of a population model. This tradeoff introduces an alternative strategy for the pathogen: a low‐transmission, low‐variability type can coexist with the high‐transmission type favoured by classical non‐heterogeneity models. In addition, this tradeoff can help explain the extensive phenotypic variation we observed in field‐collected pathogen isolates, in traits affecting virus fitness including transmission and environmental persistence. Similar heterogeneity tradeoffs might be a general mechanism promoting phenotypic variation in any pathogen for which hosts vary continuously in susceptibility.     

MicroRNA与细胞信号转导通路研究进展

成熟的microRNA(miRNA)是一种长约22 nt的非编码RNA,通过与靶基因的3′非翻译区(3′UTR)结合来调控靶基因的表达。直至目前,在不同物种中发现的miRNA达6 397个。miRNA的发现为基因表达调控研究打开了新的窗口。目前研究者不仅证实miRNA在生物体生长、发育和疾病发生等过程中发挥着重要的作用,而且开始进一步探寻其发挥作用的分子机理。综述了miRNA与细胞信号转导途径之间的关系,从而有助于从基因水平上理解疾病的发生机制,为疾病的诊断、治疗提供依据。     

The emerging role of small non-coding RNA in renal cell carcinoma

Noncoding RNAs are transcribed in the most regions of the human genome, divided into small noncoding RNAs (less than 200 nt) and long noncoding RNAs (more than 200 nt) according to their size. Compelling evidences suggest that small noncoding RNAs play critical roles in tumorigenesis and tumor progression, especially in renal cell carcinoma. MiRNA, the most famous small noncoding RNA, has been comprehensively explored for its fundamental role in cancer. And several miRNA-based therapeutic strategies have been applied to several ongoing clinical trials. However, piRNAs and tsRNAs, have not received as much research attention, because of several technological limitations. Nevertheless, some studies have revealed the presence of aberration of piRNAs and tsRNAs in renal cell carcinoma, highlighting a potentially novel mechanism for tumor onset and progression. In this review, we provide an overview of three classes of small noncoding RNA: miRNAs, piRNAs and tsRNAs, that have been reported dysregulation in renal cell carcinoma and have the potential for advancing diagnosis, prognosis and therapeutic applications of this disease.     

Early host gene expression responses to a Salmonella infection in the intestine of chickens with different genetic background examined with cDNA and oligonucleotide microarrays

So far the responses of chickens to Salmonella have not been studied in vivo on a whole genome-wide scale. Furthermore, the influence of the host genetic background on gene expression responses is unknown. In this study gene expression profiles in the chicken (Gallus gallus) intestine of two genetically different chicken lines were compared, 24 h after a Salmonella enteritidis inoculation in 1-day-old chicks. The two chicken lines differed in the severity of the systemic infection. For gene expression profiles, a whole genome oligonucleotide array and a cDNA microarray were used to compare both platforms. Genes upregulated in both chicken lines after the Salmonella infection had a function in the innate immune system or in wound healing. Genes regulated after the Salmonella infection in one chicken line encoded proteins involved in inflammation, or with unknown functions. In the other chicken line upregulated genes encoded proteins involved in acute phase response, the fibrinogen system, actin polymerisation, or with unknown functions. Some of the host gene responses found in this study are not described before as response to a bacterial infection in the intestine. The two chicken lines reacted with different intestinal gene responses to the Salmonella infection, implying that it is important to use chickens with different genetic background to study gene expression responses.     

Genome sequencing and functional characterization of the non-pathogenic Klebsiella pneumoniae KpGe bacteria

Klebsiella pneumoniae is an extensively studied human pathogen responsible for a wide variety of infections. Dictyostelium discoideum is a model host organism employed to study many facets of the complex interactions between phagocytic cells and bacteria. Historically, a non-pathogenic strain of K. pneumoniae has been used to feed Dictyostelium amoebae, and more recently to study cellular mechanisms involved in bacterial recognition, ingestion and killing. Here we provide the full genome sequence and functional characterization of this non-pathogenic KpGe strain.     

RNA interference: Biology and prospects of application in biomedicine and biotechnology

RNA interference is one of the most important mechanisms regulating gene expression. Small interfering RNAs (siRNAs) play an essential role in cell defense against virus infection or retrotransposons. The use of siRNAs gives wide opportunities for treating virus infections and cancer. RNA interference allows rapid construction of monogenic functional knockouts, thereby providing a convenient tool for researchers. The review considers the current views of the mechanisms of RNA interference and modern approaches to its practical application.     

Host resistance and pathogen infectivity in host populations with varying connectivity

Theory predicts that hosts and pathogens will evolve higher resistance and aggressiveness in systems where populations are spatially connected than in situations in which populations are isolated and dispersal is more local. In a large cross‐inoculation experiment we surveyed patterns of host resistance and pathogen infectivity in anther‐smut diseased Viscaria alpina populations from three contrasting areas where populations range from continuous, through patchy but spatially connected to highly isolated demes. In agreement with theory, isolated populations of V. alpina were more susceptible on average than either patchily distributed or continuous populations. While increased dispersal in connected systems increases disease spread, it may also increase host gene flow and the potential for greater host resistance to evolve. In the Viscaria–Microbotryum system, pathogen infectivity mirrored patterns of host resistance with strains from the isolated populations being the least infective and strains from the more resistant continuous populations being the most infective on average, suggesting that high resistance selects for high infectivity. To our knowledge this study is the first to characterize the impacts of varying spatial connectivity on patterns of host resistance and pathogen infectivity in a natural system.