Trichinella spiralis: phospholipase in challenged mice and rats

Mice challenged with 400 larvae of T. spiralis showed greatly elevated phospholipase levels in tissues of the small intestine from 5 to 29 days after infection, after which the levels returned to those of the uninfected controls. Related to these rises in enzyme levels were greatly increased numbers of eosinophils in the bone marrow. Increases strikingly above those in the controls were noted from 8 to 20 days after infection. In rats challenged with 3000 larvae, the enzyme levels were elevated from 4 to 18 days, and the eosinophils were increased during the same periods. A working hypothesis is proposed to explain these phenomena.     

Metaplasia of the lung alveolar epithelium in mice repeatedly challenged with influenza virus

Mice were repeatedly infected intranasally with increasing doses of influenza virus. A correlation was observed between the incidence of metaplasia of the lung alveolar epithelium and serum antibody levels.     

Adoptive immunity in mice challenged with L1210/DTIC clones

Summary New antigenic specificities, not detectable on parental cells, have been induced by many investigators in mouse lymphomas by treatment with the antitumor agent 5(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC). The antigens are transmissible, after withdrawal of the drug treatment, as an inheritable character. The mechanism of induction, the molecular nature, and the number of the new antigenic specificities have not been completely elucidated. Four clones from murine leukemia L1210 isolated and expanded in vitro were treated in vivo with DTIC and the new sublines were studied in detail. The four drug-treated sublines studied exhibited strong immunogenicity since they were rejected by syngeneic animals. Immunosuppressed animals challenged with 10⁷ A/DTIC or P/DTIC cells were reciprocally protected by the adoptive transfer of spleen cells from donors that had rejected a lethal challenge of A/DTIC or P/DTIC clones. In a similar fashion, the adoptive transfer of spleen cells obtained from animals that had rejected the Q/DTIC or the R/DTIC clones protected immunosuppressed mice challenged with Q/DTIC or R/DTIC cells. No antitumor activity was observed in cross-protective schedules other than those indicated. It was been concluded that (a) the L1210 leukemia line does not have antigenic cells, (b) four DTIC-treated clone sublines were rejected by compatible hosts, and (c) two mutually exclusive sets of antigens were expressed in four antigenic clone sublines.Research supported in part by P.F.O. Contract Grant from C. N. R., Rome, Italy     

Physiological and histopathological changes in the intestines of mice challenged with S. typhi

Transport of Na+, Cl-, Ca2+ and 3-0-methyl-D-glucose (a non-metabolizable analogue of D-glucose) was worked out in control, infected and immunized-infected animals along with histopathological studies of the intestines in these groups. There was significant decrease (p less than 0.01) in net absorption of Na+ and Cl- in the infected group as compared to that in the control group. There was also a significant decrease (p less than 0.01) in 3-0-methyl-D-glucose uptake in the infected group. However, no change was found in the immunized group in any of the electrolytes and non-metabolizable analogue of D-glucose. These findings correlated well with the histopathological studies as the infected intestines showed complete disorganization of mucosal tissues with loss of epithelial cells from the villi whereas the mucosal lining and epithelial cells from the intestines of immunized mice were normal looking.     

Sublethal infection with Salmonella Enteritidis by the natural route induces intestinal and joint inflammation in mice

Reactive arthritis (ReA) is a sterile inflammation triggered by a distal mucosal infection, which suggests a contribution from bacterial products. Investigation on the pathogenesis of ReA is difficult because of the limited studies that can be performed in humans; therefore the availability of animal models is crucial. We hereby describe a murine model for studying the early stages of Salmonella-induced ReA. BALB/c mice infected by the natural route with a sublethal dose of S. Enteritidis showed long lasting gut inflammation, synovitis in the knee joint and a significant increase of CD4+ lymphocytes in the draining popliteal lymph nodes. S. Enteritidis infection induced histological changes in intact knees and exacerbated inflammation in previously damaged joints. Experiments performed with S. Enteritidis ΔinvG mutant suggest that the proinflammatory signalling mediated by Salmonella TTSS-1 in the gut is required for the induction of joint sequelae. Since this model is highly reproducible and easy to perform, it provides great potential for investigating both host and bacterial contributions to the early stages of ReA.     

Specific immunoglobulin response in mice immunized with porins and challenged with Salmonella typhi

Specific antiporin antibody (IgG, IgM, and IgA) response was studied in control, infected, immunized-infected, and immunized mice. The activity of specific IgG immunoglobulins was found to be the highest in immunized and immunized-infected groups in which 87.5% protection had been observed by laboratory potency test in mice; the next-highest activities were those of IgM and IgA immunoglobulins. However, in the infected group the activity of specific IgM and IgG immunoglobulins was almost similar.     

Humoral immunity and protection of mice challenged with homotypic or heterotypic parvovirus.

BACKGROUND AND OBJECTIVES: Two serotypes of autonomously replicating parvoviruses infect laboratory mice. Genome regions coding for the nonstructural proteins of minute virus of mice [MVM] and mouse parvovirus [MPV] are almost identical, whereas capsid-coding sequences are divergent. We addressed these questions: Does humoral immunity confer protection from acute infection after challenge with homotypic or heterotypic parvovirus, and if it confers protection against acute MPV infection, does it also protect against persistent MPV infection? METHODS: Infant mice without maternal antibody or antibody to MVM or MPV and young adult mice given normal mouse serum or antibody to MVM or MPV were challenged with homotypic or heterotypic virus. In situ hybridization with target tissues was the indicator of infection. RESULTS: Humoral immunity failed to confer protection against acute heterotypic parvovirus infection. In passive transfer studies, MPV DNA was observed occasionally in lymph nodes, intestine, or the spleen of MPV-challenged mice given homotypic antibody and kept for 6 or 28 days. Variable proportions of mice given MPV antibody and homotypic challenge had viral DNA in lymphoid tissues 56 days after virus inoculation. CONCLUSION: A mouse or colony that has sustained infection with MVM or MPV is probably fully susceptible to infection with the heterotypic virus.     

Experimental toxicoinfection in infant mice challenged with spores of Clostridium botulinum type E

Conventionally raised suckling mice were given 10(7) spores of a strain of Clostridium botulinum type E. Most but not all infant mice aged 8 through 19 days at the time of administration died after developing symptoms typical of botulism. However, none of the infant mice challenged with the spores at dose levels lower than 10(6) spores/mouse developed illness.     

Enhanced macrophage activity in granulomatous lesions of immune mice challenged with Mycobacterium tuberculosis

In this study, we evaluated the cellular influx and cytokine environment in the lungs of mice made immune by prior vaccination with Mycobacterium bovis bacillus Calmette-Guérin compared with control mice after infection with Mycobacterium tuberculosis to characterize composition of protective lesions in the lungs. Immune mice controlled the growth of the M. tuberculosis challenge more efficiently than control mice. In immune animals, granulomatous lesions were smaller and had a more lymphocytic core, less foamy cells, less parenchymal inflammation, and slower progression of lung pathology than in lungs of control mice. During the chronic stage of the infection, the bacterial load in the lungs of immune mice remained at a level 10 times lower than control mice, and this was associated with reduced numbers of CD4P(+P) and CD8P(+P) T cells, and the lower expression of protective (IL-12, IFN-gamma), inflammatory (TNF-alpha), immunoregulatory (GM-CSF), and immunosuppressive (IL-10) cytokines. The immune mice had higher numbers of CD11b- CD11c(high) DEC-205(low) alveolar macrophages, but lower numbers of CD11b+ CD11c(high) DEC-205(high) dendritic cells, with the latter expressing significantly lower levels of the antiapoptotic marker TNFR-associated factor-1. Moreover, during the early stage of chronic infection, lung dendritic cells from immune mice expressed higher levels of MHC class II and CD40 molecules than similar cells from control mice. These results indicate that while a chronic disease state is the eventual outcome in both control and immune mice infected with M. tuberculosis by aerosol exposure, immune mice develop a protective granulomatous lesion by increasing macrophage numbers and reduced expression of protective and inflammatory cytokines.     

自然感染途径建立肺炎链球菌感染性肺炎小鼠模型

目的探索自然感染途径制备肺炎链球菌感染性肺炎小鼠模型的方法,为肺炎链球菌性肺炎的相关研究提供实验基础。方法肺炎链球菌标准菌株(CMCC 31203)经血平板培养18 h后配成2麦氏浊度。小鼠浅麻醉状态下,破损鼻黏膜,滴注一定量肺炎链球菌菌液。于3、7、14和21 d分别处死小鼠,取肺脏进行组织病理学观察,确定肺炎小鼠模型制备的最佳方式。结果鼻黏膜破损组小鼠3 d时肺泡间隔内毛细血管扩张,肺泡腔内以红细胞和纤维素渗出为主;7 d时病变以纤维素和中性粒细胞浸润为主;14 d时肺泡腔内渗出减少,炎症开始减轻;21 d时肺脏外观趋于正常,肺泡腔内渗出物质基本溶解吸收。结论以3×107CFU的肺炎链球菌菌液通过破损的鼻黏膜感染7 d时可以制备出比较典型、稳定的肺炎小鼠模型。     

Oral immunization of BALB/c mice by intragastric delivery of Streptococcus gordonii-expressing Giardia cyst wall protein 2 decreases cyst shedding in challenged mice

Giardia lamblia (Giardia duodenalis or Giardia intestinalis) is a protozoan parasite of vertebrates with broad host specificity. Specific antibodies directed against cyst antigens can interfere with the cyst wall-building process. In this study, we engineered Streptococcus gordonii to express a 26 kDa fragment of cyst wall protein 2 (CWP2), containing a relevant B cell epitope, on the cell surface. This is the first report of S. gordonii expressing a protein of parasite origin. As S. gordonii was intended for intestinal delivery of CWP2, it was determined that this oral commensal bacterium is able to persist in the murine intestine for 30 days. Immunization with recombinant streptococci expressing the 26 kDa fragment resulted in higher antibody levels. Specific anti-CWP2 IgA antibodies were detected in fecal samples and anti-CWP2 IgG antibodies were detected in serum demonstrating the efficacy of S. gordonii for intragastric antigen delivery. In a pilot challenge experiment, immunized mice demonstrated a significant 70% reduction in cyst output.     

Antileishmanial activity of a formulation of 2-n-propylquinoline by oral route in mice model

2-n-propylquinoline is presently a drug-candidate for the treatment of visceral leishmaniosis in pre-clinical development. As this compound is in an oily state, it needs to be formulated and the objectives of this study are: to prepare a formulation; to demonstrate that the new salted formulation did not alter the activity of the active ingredient; and finally, that this activity was quite good compared to the reference oral drug, miltefosine. Therefore, a 2-n-propylquinoline formulation, as camphorsulfonic salt, was prepared and characterised. On the Leishmania donovani / Balb/c mice model, a treatment by oral route at 60 μmoles/kg/day for ten consecutive days with this formulation was compared to 2-n-propylquinoline alone and to miltefosine, the oral reference drug. The salt formulation did not alter the activity of the 2-n-propylquinoline. The formulation reduced the parasite burden of 76% compared to 89% for miltefosine (not significant). The characteristics of this formulation results in a suitable drugability of 2-n-propylquinoline for further studies.     

Acute inflammatory response in the stomach of BALB/c mice challenged with coccoidal Helicobacter pylori

An experimental murine model was used to verify the viability and pathogenicity of coccoid Helicobacter pylori. For this purpose, 27 BALB/c mice were inoculated intragastrically with 1 ml broth culture (10(8)organisms/ml) of a coccoid H. pylori clinical isolate. The animals were divided into two groups. Nine were infected on a one-time basis (GA1) and 18 were infected on two consecutive days (GA2). Other 27 mice were inoculated with Brucella broth and divided in the same way; they composed the control group. Mice were killed at 2, 3, 7, 14 and 21 days post inoculation (pi). Fragments of stomach and duodenum were collected, fixed with 12% formalin and stained by hematoxilin-eosin and Giemsa for histopathological examination. Until the 14th()day, only reinfected mice had mild-to-moderate inflammatory infiltrate in the stomach. The infiltration was predominantly lymphomonocytic, although plasma cells and eosinophils could be seen. However, at 21st day, severe eosinophilic infiltration was present in the lamina propria and submucosa of gastric corpus. In subgroup GA1, animals presented lymphomonocytic infiltration in the stomach from 14th()day pi. Our results showed that coccoid H. pylori was able to induce an acute inflammatory response in stomach of reinfected mice since the initial periods of infection.