Resistance to Bacterial Infection Induced by Statolon and Pyran

The antibacterial properties of statolon and pyran were compared with those of bacterial endotoxin and found to be similar. Although high resistance was transient, it was followed by immunity of the same order as in mice infected without pre-treatment with the interferon inducers.     

局部力学刺激对黄瓜系统抗病性的诱导

病原真菌在侵入植物细胞过程中,除了分泌化学物质外还通过物理挤压细胞产生力学作用.用压应力作为力学信号,研究了局部力学刺激对黄瓜系统抗病性的诱导.结果表明,力学刺激可以诱导黄瓜系统抗病性的产生.当细胞壁与质膜间的黏附被Arg-Gly-Asp(RGD)阻断后,力学刺激对黄瓜系统抗病性的诱导几乎完全被减除.通过薄层色谱和液相色谱分析,发现力学刺激可以使植保素含量明显增加.这表明黄瓜植保素的积累可能是力学刺激诱导其产生抗性的原因之一.而细胞壁与质膜间的黏附被RGD阻断后,力学刺激只能诱导植保素的部分积累.即力学刺激对植保素积累的诱导依赖于细胞膜与细胞壁间的黏附.     

Nonspecific Stimulation of Antibacterial Resistance by a Synthetic Thymic Factor (FTS) in Mice

Treatment of mice with 0.01–1 μg of a synthetic serum thymic factor (FTS) significantly increased their resistance to lethal doses (1–5 × 10⁶ organisms) of Salmonella typhimurium LT2 (LT2). At least seven injections of FTS were necessary for induction of resistance, since the effects of one to three injections were variable. FTS additively potentiated the protective immunity to LT2 induced by immunization with an avirulent mutant of LT2, irrespective of the structural components of the cell wall lipopolysaccharides of the mutants, which are basically correlated with their immunogenicity and virulence. Activated macrophages may have a direct role in the induction of host resistance, since peritoneal macrophages from FTS-treated DBA/2 mice which are resistant to the doses of LT2 used could by themselves retard bacterial growth in vitro, whereas those from CBA/N mice which are relatively susceptible to LT2 did not inhibit bacterial growth without intervention of FTS-treated syngeneic T cells.     

Temporal and Anatomical Host Resistance to Chronic Salmonella Infection Is Quantitatively Dictated by Nramp1 and Influenced by Host Genetic Background

The lysosomal membrane transporter, Nramp1, plays a key role in innate immunity and resistance to infection with intracellular pathogens such as non-typhoidal Salmonella (NTS). NTS-susceptible C57BL/6 (B6) mice, which express the mutant Nramp1^D169 allele, are unable to control acute infection with Salmonella enterica serovar Typhimurium following intraperitoneal or oral inoculation. Introducing functional Nramp1^G169 into the B6 host background, either by constructing a congenic strain carrying Nramp1^G169 from resistant A/J mice (Nramp-Cg) or overexpressing Nramp1^G169 from a transgene (Nramp-Tg), conferred equivalent protection against acute Salmonella infection. In contrast, the contributions of Nramp1 for controlling chronic infection are more complex, involving temporal and anatomical differences in Nramp1-dependent host responses. Nramp-Cg, Nramp-Tg and NTS-resistant 129×1/SvJ mice survived oral Salmonella infection equally well for the first 2–3 weeks, providing evidence that Nramp1 contributes to the initial control of NTS bacteremia preceding establishment of chronic Salmonella infection. By day 30, increased host Nramp1 expression (Tg>Cg) provided greater protection as indicated by decreased splenic bacterial colonization (Tg<Cg). However, despite controlling bacterial growth within MLN as effectively as 129×1/SvJ mice, Nramp-Cg and Nramp-Tg mice eventually succumbed to infection. These data indicate: 1) discrete, anatomically localized host resistance is conferred by Nramp1 expression in NTS-susceptible mice, 2) restriction of systemic bacterial growth in the spleens of NTS-susceptible mice is enhanced by Nramp1 expression and dose-dependent, and 3) host genes other than Nramp1 also contribute to the ability of NTS-resistant 129×1/SvJ mice to control bacterial replication during chronic infection.     

A Potato Virus X Resistance Gene Mediates an Induced,Nonspecific Resistance in Protoplasts

The Rx locus in potato controls extreme resistance to most isolates of potato virus X (PVX). The resistance is expressed in whole plants and in protoplasts. Rx-mediated resistance in protoplasts causes reduced accumulation of all PVX RNA species, including the (-) strand RNA after a lag of 8 hr postinoculation. In work reported elsewhere, we have shown that the Rx-breaking property of PVXHB was associated with the coat protein gene of PVXUK3 and PVXCP4. Here, we describe how a frameshift mutation in the coat protein gene had no effect on Rx resistance breaking but compromised the Rx-mediated resistance to PVXCP4. We also describe how in coinoculation experiments, the Rx-mediated resistance could be induced to affect PVXHB or cucumber mosaic virus (CMV). In these experiments, PVXHB or CMV was coinoculated to protoplasts (Rx genotype) together with an isolate of PVX, which is affected by Rx. We interpret this data to indicate that Rx-mediated resistance is induced when the PVX coat protein is produced in the infected cells and that the induced resistance mechanism is effective against viruses unrelated to PVX.     

Enhancement by Recombinant Human Interleukin 2 of Host Resistance to Toxoplasma gondii Infection in Pregnant Mice

The lymphokine production by pregnant mice infected with a lethal dose of Toxoplasma gondii was evaluated in comparison with that by virgin mice infected with a sublethal dose of this protozoan parasite. Splenocytes taken from mice before and on the day after infection produced considerable amounts of IL-2 in response to concanavalin A (Con A) stimulation, but the titers rapidly declined in both pregnant and virgin mice as infection progressed. A trace amount or undetectable level of IL-2 was produced by splenocytes from acutely infected mice when stimulated with Toxoplasma lysate antigen (TLA). In contrast to the kinetics of IL-2 production, the levels of IFN-γ produced by splenocytes cultured with Con A or TLA increased steadily in the later stage of infection in both pregnant and virgin mice. Thus, the response to Con A or TLA of splenocytes to produce IL-2 and IFN-γ differed strikingly in acute toxoplasmosis in mice. The administration of rHuIL-2 resulted in a significant decrease in the mortality of pregnant mice infected with a lethal dose of Toxoplasma. The combination of rHuIL-2 and rMuIFN-γ increased the survival rate slightly but not significantly compared with pregnant mice receiving either rHuIL-2 or rMuIFN-γ. Moreover, exogenously administered rHuIL-2 enhanced the production of both IFN-α and IFN-γ in the bloodstreams of pregnant mice, in accordance with the decreased mortality. These results indicate that IL-2 may play a significant role in modulating the host defense against Toxoplasma infection in pregnant mice.     

Virus Resistance Induced with Mannan Sulphates in Hypersensitive Host Plants

Mannan sulphates (MS), obtained by sulphatation of extracellular linear mannan (LM) from Rhodotorula rubra, induced resistance to tobacco mosaic virus (TMV) in hypersensitive plants, retained in isolated protoplasts. MS-induced resistance in tobacco is accompanied by a marked increase of lytic processes in cells and a decrease of total (acidic and alkaline) protein content. In addition to this, new protein components, including PR-proteins and antiviral substances, of the inhibitor of virus replication (IVR) type, appeared in treated plant tissues. MS-induced resistance resembles localized resistance induced by TMV in hypersensitive tobacco plants and could serve as an experimental model for study of the latter.     

Resistance to Coliphage Infection Induced in Escherichia coli by Growth in the Presence of a Surfactant

Heavy slime exudates surrounding Escherichia coli cells grown in media containing 1% sodium dodecybenzene sulfonate apparently block adsorption of coliphages to susceptible strains.     

UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii

UNC93B1 associates with Toll-Like Receptor (TLR) 3, TLR7 and TLR9, mediating their translocation from the endoplasmic reticulum to the endolysosome, hence allowing proper activation by nucleic acid ligands. We found that the triple deficient ‘3d’ mice, which lack functional UNC93B1, are hyper-susceptible to infection with Toxoplasma gondii. We established that while mounting a normal systemic pro-inflammatory response, i.e. producing abundant MCP-1, IL-6, TNFα and IFNγ, the 3d mice were unable to control parasite replication. Nevertheless, infection of reciprocal bone marrow chimeras between wild-type and 3d mice with T. gondii demonstrated a primary role of hemopoietic cell lineages in the enhanced susceptibility of UNC93B1 mutant mice. The protective role mediated by UNC93B1 to T. gondii infection was associated with impaired IL-12 responses and delayed IFNγ by spleen cells. Notably, in macrophages infected with T. gondii, UNC93B1 accumulates on the parasitophorous vacuole. Furthermore, upon in vitro infection the rate of tachyzoite replication was enhanced in non-activated macrophages carrying mutant UNC93B1 as compared to wild type gene. Strikingly, the role of UNC93B1 on intracellular parasite growth appears to be independent of TLR function. Altogether, our results reveal a critical role for UNC93B1 on induction of IL-12/IFNγ production as well as autonomous control of Toxoplasma replication by macrophages.     

Rhadinovirus Host Entry by Co-operative Infection

Rhadinoviruses establish chronic infections of clinical and economic importance. Several show respiratory transmission and cause lung pathologies. We used Murid Herpesvirus-4 (MuHV-4) to understand how rhadinovirus lung infection might work. A primary epithelial or B cell infection often is assumed. MuHV-4 targeted instead alveolar macrophages, and their depletion reduced markedly host entry. While host entry was efficient, alveolar macrophages lacked heparan - an important rhadinovirus binding target - and were infected poorly ex vivo. In situ analysis revealed that virions bound initially not to macrophages but to heparan⁺ type 1 alveolar epithelial cells (AECs). Although epithelial cell lines endocytose MuHV-4 readily in vitro, AECs did not. Rather bound virions were acquired by macrophages; epithelial infection occurred only later. Thus, host entry was co-operative - virion binding to epithelial cells licensed macrophage infection, and this in turn licensed AEC infection. An antibody block of epithelial cell binding failed to block host entry: opsonization provided merely another route to macrophages. By contrast an antibody block of membrane fusion was effective. Therefore co-operative infection extended viral tropism beyond the normal paradigm of a target cell infected readily in vitro; and macrophage involvement in host entry required neutralization to act down-stream of cell binding.     

Nonspecific Factors Involved in Attachment of Entomopathogenic Deuteromycetes to Host Insect Cuticle

The attachment of the conidia of the insect-pathogenic fungi Nomuraea rileyi, Beauveria bassiana, and Metarrhizium anisopliae to insect cuticle was mediated by strong binding forces. The attachment was passive and nonspecific in that the conidia adhered readily to both host and nonhost cuticle preparations. The hydrophobicity of the conidial wall and the insect epicuticle appeared to mediate the adhesion process. Detergents, solvents, and high-molecular-weight proteins known to neutralize hydrophobicity reduced conidial binding when added to conidium-cuticle preparations. However, these chemicals did not remove the hydrophobic components from the epicuticle or from conidial preparations. The outer surface of the conidium consists of a resilient layer of well-organized fascicles of rodlets. Intact rodlets extracted from B. bassiana conidia bound to insect cuticle and exhibited the hydrophobicity expressed by intact conidia. Both electrostatic charges and various hemagglutinin activities were also present on the conidial surface. However, competitive-inhibition studies indicated that these forces played little, if any, role in the adhesion process.     

Host Cytokine Responses Induced after Overnight Stimulation with Novel M. tuberculosis Infection Phase-Dependent Antigens Show Promise as Diagnostic Candidates for TB Disease

Background

We previously identified Mycobacterium tuberculosis (M.tb) antigen-induced host markers that showed promise as TB diagnostic candidates in 7-day whole blood culture supernatants. The aim of the present study was to evaluate the utility of these markers further, and cross-compare results with short-term antigen stimulated and unstimulated culture supernatants.

Methods

We recruited 15 culture confirmed TB cases and 15 non-TB cases from a high-TB endemic community in Cape Town, South Africa into a pilot case-control study from an on-going larger study. Blood samples collected from study participants were stimulated with 4 M.tb antigens that were previously identified as promising (ESAT6/CFP10 (early secreted), Rv2029c (latency), Rv2032 (latency) and Rv2389c (rpf)) in a 7-day or overnight culture assay. Supernatants were also collected form the standard QuantiFERON In Tube (QFT-IT) test. The levels of 26 host markers were evaluated in the three culture supernatants using the Luminex platform.

Results

The unstimulated levels of CRP, Serum amyloid P (SAP) and serum amyloid A (SAA) and ESAT-6/CFP-10 specific IP-10 and SAA were amongst the best discriminatory markers in all 3 assays, ascertaining TB with AUC of 72–84%. Four-marker models accurately classified up to 92%, 100% and 100% of study participants in the overnight, 7-day and Quantiferon culture supernatants, respectively, after leave-one-out cross validation.

Conclusion

Unstimulated and antigen-specific levels of CRP, SAA, IP-10, MMP-2 and sCD40L hold promise as diagnostic candidates for TB disease in short-term stimulation assays. Larger studies are required to validate these findings but the data suggest that antigen-specific cytokine production and in particular mutimarker biosignatures might contribute to future diagnostic strategies.     

Augmentation of Host Resistance against Bacterial Infection by Treatment with Leustroducsin B,a New CSF Inducer

We tested the in vivo activity of leustroducsin B (LSN B), a new colony-stimulating factor (CSF) inducer isolated from the culture broth of Streptomyces platensis, with mice infected with Escherichia coli. Treatment with LSN B augmented the host resistance to lethal infection of E. coli at doses between 0.1 mg/kg and 1 mg/kg. Serum interleukin-6 (IL-6) levels were found to increase after this treatment, and superoxide anion generation of neutrophils was enhanced in vivo, suggesting that LSN B augmented the host resistance at least in part by inducing IL-6, which subsequently enhanced the bactericidal activity of the neutrophils.     

DNA微阵列技术在细菌感染后宿主反应研究中的应用

感染性疾病是病原微生物和宿主紧密相互作用的结果。深入理解宿主对病原微生物感染发生反应的分子基础是预防感染性疾病发生和组织损伤的必要条件。本文通过介绍体内、体外2种感染模型中宿主对细胞内和细胞外致病菌感染后的基因表达谱变化,简述了DNA微阵列技术在病原菌一宿主相互作用中宿主反应研究中的应用。