Immunosuppressive activity in serum from mice infected with Nematospiroides dubius following passive serum transfer

Dobson C. and Cayzer C. J. R. 1982. Immunosuppressive activity in serum from mice infected with Nematospiroides dubius following passive serum transfer. International Journal for Parasitology12: 561–566. Anti-N. dubius antibody titres increased with time after primary and secondary infections with 100 larvae in mice and 4 days after anthelmintic termination of a 28 day infection. Mice injected with serum from infected mice harboured fewer, smaller worms with reduced fecundities compared with control mice; the difference was greater with serum from donors given two compared with those given one infection.Mice injected with serum from donors infected for 14 days had fewer N. dubius than recipients of serum from mice infected for 28 days. Serum taken from mice 4 days after termination of a primary infection of 28 days duration was more protective when passively transferred to mice than serum from mice infected for 28 days. Serum from mice infected with 50 N. dubius larvae was more protective than serum, with a higher anti-N. dubius antibody titre, from, mice infected with 400 larvae. These observations are discussed in relation to immunosuppressive activities in the donated serum and associated with N. dubius.     

Influence of serial passage on the infectivity and immunogenicity of Nematospiroides dubius in mice

Dobson C. and Owen M. E. 1977. Influence of serial passage on the infectivity and immunogenicity of Nematospiroides dubius in mice. International Journal for Parasitology7: 463–466. The infectivity of Nematospiroides dubius was increased for Quackenbush (Q) mice by ten serial passages through this host. At the same time C(In3)H mice became more refractory to infection with successive Q generations of the parasite. Both strains of mice rejected the most highly selected parasites more readily than parasites from the earlier generations. These responses were shown to be immunological in nature by infections in hypothymic Balb/c CBA nu/nu and nu/+ mice and to be dose dependent. The selection of N. dubius for increased infectivity in Q mice enhanced its immunogenicity in this and other mouse strains possibly because of increased genetic homogenicity in the selected populations. N. dubius selected for Q mice showed a degree of immunologieal adaptation to Q but not to C₃H mice.     

Nematospiroides dubius in mice selected for liability to infection: Modification of parasite biology through host selection

Brindley P. J. and Dobson C. 1982. Nematospiroides dubius in mice selected for liability to infection: modification of parasite biology through host selection. International Journal for Parasitology12: 573–578. Mice selected as liable (L) and refractory (R) over ten generations voided significantly more and less Nematospiroides dubius eggs compared with randomly mated (Rd) mice after primary infections with 100 larvae. There was little difference between the number of parasite eggs voided g^?1 faeces (epg) by individual mice on day 14 compared with day 15 after infection.However there was a significant diurnal variation in the egg values for individual mice but the mean differences observed between the R, Rd and L mice were maintained over a 24 h period. There was a strong correlation between both the total number and the number of female worms, surviving 21 days after infection, and the mean epg 14 and 15 days after infection. Female N. dubius produced more eggs in L mice and fewer eggs in R mice compared with worms in Rd mice. Similarly, worms grew longer in L mice and were shorter in R mice compared with parasites in Rd mice.     

Transfer of immunity against Trichuris muris in the mouse by serum and cells

Transfer of immunity against Trichuris muris in the mouse by serum and cells. Internationaljournal for Parasitology 3: 717–722. A protective immunity against the nematode Trichuris muris was transferred with antiserum and cells taken from immunized mice. Immunity was transferred most reliably by cells, especially mesenteric lymph node cells, but most effectively by serum. The protective capacity of serum and cells taken from the same mice was not always related. Multiple immunization of the donors did not markedly increase protection in the recipients.     

Differential expression of VGLUT3 in laboratory mouse strains: Impact on drug‐induced hyperlocomotion and anxiety‐related behaviors

The atypical vesicular glutamate transporter VGLUT3 is present in subpopulations of GABAergic interneurons in the cortex and the hippocampus, in subgroups of serotoninergic neurons in raphe nuclei, and in cholinergic interneurons in the striatum. C56BL/6N mice that no longer express VGLUT3 (VGLUT3^?/?) display anxiety‐associated phenotype, increased spontaneous and cocaine‐induced locomotor activity and decreased haloperidol‐induced catalepsy. Inbred mouse strains differ markedly in their sensitivity to anxiety and behavioral responses elicited by drugs. The purpose of this study was to investigate strain differences in VGLUT3 expression levels and its potential correlates with anxiety and reward‐guided behaviors. Five inbred mouse lines were chosen according to their contrasted anxiety and drugs sensitivity: C57BL/6N, C3H/HeN, DBA/2J, 129/Sv, and BALB/c. VGLUT3 protein expression was measured in different brain areas involved in reward or mood regulation (such as the striatum, the hippocampus, and raphe nuclei) and genetic variations in Slc17a8, the gene encoding for VGLUT3, have been explored. These five inbred mouse strains express very different levels of VGLUT3, which cannot be attributed to the genetic variation of the Slc17a8 locus. Furthermore, mice behavior in the open field, elevated plus maze, spontaneous‐ and cocaine‐induced locomotor was highly heterogeneous and only partially correlated to VGLUT3 levels. These data highlight the fact that one single gene polymorphism could not account for VGLUT3 expression variations, and that region specific VGLUT3 expression level variations might play a key role in the modulation of discrete behaviors.     

Combination of CpG-oligodeoxynucleotides with recombinant ROP2 or GRA4 proteins induces protective immunity against Toxoplasma gondii infection

Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN) have been characterized as Th1-promoting immunopotentiators, an adjuvant activity desirable for vaccination against intracellular parasites like Toxoplasma gondii. In an attempt to find new antigen–adjuvant combinations that enhance the immunogenicity of antigen candidates for toxoplasma vaccines, we analyzed the extent of protection in mice immunized with ROP2 and GRA4 recombinant proteins when co-administered with CpG-ODN. Both GRA4 + CpG-ODN and ROP2 + CpG-ODN formulations were shown to induce a strong humoral Th1-biased response characterized by a high IgG_2a to IgG₁ antibody ratio. Both vaccination regimens led to increased secretion of IFN-γ and IL-10, and negligible amounts of IL-4, upon specific re-stimulation of spleen cells from these groups of mice. After a non-lethal challenge with tissue cysts of a moderately virulent strain, only the brains from mice vaccinated with ROP2 or GRA4 in combination with CpG-ODN showed a significant reduction (63% and 62%, respectively) in their parasite load compared to the controls. The rate of protection obtained with GRA4 + ROP2 + CpG-ODN resulted equivalent (66%) to those achieved with the single antigens plus CpG-ODN. Taken together, these results indicate that CpG-ODN is an important candidate adjuvant for use in potential multicomponent anti-T. gondii vaccines for animals and humans.     

Differential cellular response of resistant and susceptible rodents to the early stages of infection of Taenia taeniaeformis

Taenia taeniaeformis infection course in C3H/He and BALB/c mice (susceptible and resistant respectively to T. taeniaeformis) was compared for 10 days post-infection (p.i.). Light microscopic observation of early organisms in BALB/c revealed host cell infiltration as early as 2 days p.i. By day 4 p.i. the larvae presented an inconspicuous acellular halo and were surrounded by a dense mass of leukocytes, mainly eosinophils. The amorphous substance reacted positive for sulphated acid mucopolysaccharides. By day 6 p.i. the parasite-host interface was filled by leukocytes and fibroblasts, staining with alcian blue was limited to small areas and the parasites appeared disrupted and lightly stained by haematoxylin-eosin. At day 10 p.i. the parasite had been destroyed by the host. In rats and C3H/He mice, the parasites at day 2 p.i. were 10 μm in diameter, bounded by a larger amorphous acellular halo that reacted positive to alcian blue stain, an indication of the presence of acidic muco-polysaccharides. By day 4 p.i. the clear halo became larger and reacted strongly positive for acid mucopolysaccharides particularly close to the organism. By day 6 p.i. alcian blue positive material appeared more diffuse, covering a broad area well inside the host tissue. By this time a layer of inflammatory cells were often present at some distance from the parasite tegument. By day 10 p.i. the larvae continued growing and increasing the number of tegumental cells. The presence of sulfated acid mucopoly-saccharides around the larvae probably serves as a protective barrier for the parasite by triggering the alternative pathway of complement, consuming C3 and C5, thus preventing cell attachment and humoral antibody attack. The early destruction of the parasite by cell defense mechanism implies a major role of cellular immunity in T. taeniaeformis elimination.     

Trichinella spiralis: characterization of phage-displayed specific epitopes and their protective immunity in BALB/c mice

Trichinellosis is a global zoonosis mainly caused by Trichinella spiralis. We have previously reported that a novel Ts87 gene from the cDNA library of adult T. spiralis was cloned and expressed in a prokaryotic expression system. Vaccination with recombinant Ts87 protein (rTs87) induced a muscle larvae burden reduction in BALB/c mice by 29% in response to T. spiralis infection. In the present study, we screened a random phage-displayed peptide library using monoclonal antibody 5A3 which recognized Ts87 protein. Four positive phage clones were selected to subcutaneously immunize BALB/c mice without adjuvant. Two phage clones could effectively stimulate specific antibodies against rTs87. Mice vaccinated with these two combined phage clones showed a 28.7% worm burden reduction as compared to the control group. Therefore, the identified phage clones displayed peptides representing specific epitopes of Ts87 protein and could be considered as potential vaccine candidates for T. spiralis.