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B Hurtrel

Publications and source records attributed to B Hurtrel.

At least 55 records · Page 3Linked to original sources

Effects of suramin on the in vivo antimicrobial resistance against Listeria monocytogenes and Mycobacterium bovis (BCG) in mice.

Following one intraperitoneal injection of Suramin (400 mg/kg) in mice, biphasic alterations of the resistance to Listeria monocytogenes were observed, depending on the timing of the drug administration in relation to the intravenous challenge. Treatment with suramin, concomitantly or 1 day before, enhanced markedly the bacterial growth in spleen and liver, detected as early as 3 to 6 h after the challenge, the maximum being observed at 48 h in the liver. In contrast, an increased resistance was observed when suramin was given 8 days before the challenge. This late effect was associated with a stimulation of the mononuclear phagocyte system as measured by the increase of the spleen index and accumulation of histiocytic cells in the lymphoid organs, such as peripheral nodes. Intraperitoneal inoculation of suramin (100 mg/kg), before, during and after an intravenous injection of low dose (2 X 10(4)/mouse) of Mycobacterium bovis (BCG) in C57BL/6 and CH3 mice were followed, in both strains, by a similar increase of the mycobacterial growth in spleen and liver during the first 2 weeks. This indicates that suramin was acting on a different non specific mechanism of resistance than the one being expressed by the Bcg gene controlling the natural resistance as described recently. However, when the same schedule of suramin treatment was given to these two strains, during subcutaneous immunization with 1 X 10(7) viable BCG, a significant decrease of 48 h delayed-type hypersensitivity to tuberculin was noted 21 days later only in C57BL/6 but not in C3H mice, in which such a reaction was also of low magnitude in the infected control. The decrease of this cell-mediated immunity parameter in C57BL/6 suramin treated mice was also correlated with a higher number of viable BCG found at the challenge site and in the draining nodes.

Animals↗

Effects of suramin on the immune responses to sheep red blood cells in mice. I. In vivo studies.

The effect of Suramin on the cell-mediated delayed-type hypersensitivity (DTH) and the humoral immune responses elicited in mice by sheep erythrocytes was studied. The results show that administration of Suramin, at various times before or after antigenic sensitization, results in a profound inhibition of cell-mediated responses but has no adverse effect on antibody production. Suramin was particularly effective when given during the effector phase of DTH: mice which were treated with this drug, 4 days after immunization, at the time of skin testing, exhibit negative or low DTH responses compared to control mice. Evidence is presented that this short-term Suramin-induced suppressive effect on the expression of DTH is related to a defective recruitment, by sensitized T lymphocytes, of phagocytic cells at the site of the inflammatory reaction. In addition, when treatment with Suramin precedes by 8 days (Day -8) or by 1 hr sensitization with sheep erythrocytes for DTH, decreased DTH reactions over controls were observed. The inhibitory effect exerted by Suramin administered on Day -8 can be reversed by increasing the dose, from 10(6) to 10(8) sheep erythrocytes, of the sensitizing antigen. The possibility is discussed that, in this case, Suramin may interfere with the generation of DTH-mediating cells through a rapid degradation of antigen related to the Suramin-induced hyperplasia of the mononuclear phagocyte system. In contrast, DTH anergy in mice treated with Suramin 1 hr before sensitization is maintained regardless of the sensitizing antigen dose. Analysis of the sensitized lymphocyte population in these mice indicates that Suramin does not prevent the induction of DTH-mediating cells and suggests that the expression of these latter is inhibited by suppressive cells which are generated as a result of drug treatment.

Animals↗

Effects of suramin on the immune responses to sheep red blood cells in mice. II. In vitro studies.

The effect of Suramin on the secondary in vitro response to sheep erythrocytes (SRBC) was studied. Spleen cells from mice which were treated with Suramin immediately prior to sensitization with SRBC failed to respond to an in vitro SRBC challenge. This Suramin-induced immunosuppression is not related to a defect in macrophage or B-cell function(s). Suramin does not interfere with the induction by SRBC of radioresistant and radiosensitive helper-T-cell subpopulations. Cell separation studies, using wheat germ agglutinin, showed radiosensitive helper-T-cell function in the nonagglutinated fraction while the radioresistant helper activities are carried out by the agglutinated subpopulation. Evidence is presented that Suramin administration results in a suppressive T-cell activity which can be demonstrated in the subpopulation agglutinated by wheat germ agglutinin. The role of such suppressive T cells in the inhibitory effect exerted by Suramin on the cell-mediated delayed-type hypersensitivity response to SRBC is discussed.

Animals↗

Listeria monocytogenes infection in Biozzi mouse lines with high or low antibody responses, or with high (Hi/PHA) or low (Lo/PHA) responses to phytohemagglutinin.

Dependent and independent variables influencing natural and acquired resistance to Listeria monocytogenes in Biozzi mouse lines, genetically selected for their antibody responses, were analyzed. Variations in interline (IL) difference were shown to depend upon the inoculum dose, age, and sex of the mice used. Further, when IL differences were measured using the growth curves of L. monocytogenes, it appeared that LL mice were more resistant than HL mice, while the opposite was observed when IL differences were appreciated using the mortality rate. Attempts to analyze such apparently contradictory results showed that the predominant mechanism in LL mice was a higher natural bactericidal capacity of resident macrophages, which might be compensated for in HL mice by a higher ability to recruit blood-borne monocytes during the secondary, nonspecific phase of resistance, being reinforced and associated with a higher DTH reaction to L. monocytogenes antigen. A similar, higher antilisterial resistance was also observed in other Biozzi lines, genetically selected for their high in vitro CMI response to PHA as compared with the Lo/PHA line.

Animals↗

Comparison between immunopotency tests and specific active or passive acquired resistance against Mycobacterium tuberculosis in mice induced with three different preparations of BCG pasteur vaccine.

Tests, exploring hallmarks of cell-mediated immunity (CMI), were used in order to compare immunogenecity of same numbers of viable units from three different preparations of BCG vaccine derived from the same strain. Specific and non-specific cellular immune responses were assessed by several tests including, active and adoptive acquired resistance to Mycobacterium tuberculosis, local and systemic granuloma formation. BCG persistence in the spleen, delayed type hypersensibility (DTH) to tuberculin, immunopotentiation of DTH to sheep red blood cells, increase resistance to Listeria monocytogenes infection and occurrence of non-specific in vitro immunodepression. The ranking order of the three preparations concerning the active specific acquired resistance to tuberculosis did correlate well the ranking established for all immunopotency tests used in our study, however differences in acquired resistance were small as compared to differences observed for immunopotency tests. Moreover, adoptive transfer of same number of lymphoid cells from immune donors gave a different ranking order; the well dispersed fresh frozen (FF) vaccine being more able to induce higher adoptive protection as compared to the mechanically dispersed preparations. All these results clearly demonstrated that BCG could not be considered as single entity and that the test based on acquired resistance to M. tuberculosis or in vivo or in vitro hallmarks of CMI cannot be used as standard procedures.

Animals↗

Temperature-modulated immunogenicity to Yersinia pestis from Yersinia enterocolitica O3.

The ability of Yersinia enterocolitica O3, grown at 25 degrees C, to promote cross-immunity to Y. pestis was lost after repeated subcultures at 37 degrees C, which selected for bacterial populations having lower in vivo survival. Subculturing Y. enterocolitica O3 from 37 to 25 degrees C restored the cross-immunogenicity although the in vivo survival remained low.

Animals↗

Absence of correlation between delayed-type hypersensitivity and protection in experimental systemic candidiasis in immunized mice.

We found that in mice which had been immunized intraperitoneally with 2 x 10(8) heat-killed Candida albicans cells there was a striking temporal relationship between resistance to systemic challenge with 10(6) living C. albicans cells and a number of measurable cellular parameters of the host response. These included the emergence of delayed-type hypersensitivity and the development of granulocytosis. Since it had been shown in previous work that granulocytosis was associated with an increase in resistance when nonspecific immunostimulation was used, we performed experiments to induce delayed-type hypersensitivity without any measurable modification of the granulocyte population. Adoptive transfer of delayed-type hypersensitivity with spleen cells from immune and resistant donor mice did not produce any increase in resistance in normal recipients. When separate groups of mice were immunized intraperitoneally or subcutaneously with varying doses of heat-killed C. albicans, we found that doses of less than 10(8) cells did induce significant delayed-type hypersensitivity without any increase in granulocytosis. In such mice, as well as in animals pretreated with immunomodulators before immunization with heat-killed C. albicans, the presence of cell-mediated immunity, as measured by the delayed-type hypersensitivity test, was not associated with an increase in resistance against systemic candidiasis. On the contrary, the results suggested that cell-mediated immunity was associated with an increase in the susceptibility of these mice. The same effect on candidiasis susceptibility was observed when animals were immunized with heat-killed filamentous C. albicans.

Animals↗

Comparative effects of carrageenan on systemic candidiasis and listeriosis in mice.

Carrageenan, a toxic substance for the mononuclear phagocyte system (MPS), increase drastically the susceptibility of mice against Listeria monocytogenes challenge but induces concurrently an increasing resistance against systemic candidiasis and granulocytosis. These results corroborate the minor role played by MPS and suggest that polymorphonuclear cells play a major role in non-specific resistance of mice against systemic candidiasis.

Animals↗

Delayed-type hypersensitivity and acquired resistance to plague in mice immunized with killed Yersinia pestis and immunoregulators.

A simple reproducible footpad assay of delayed-type hypersensitivity (DTH) to Yersinia pestis was studied in mice immunized with 5 x 10(7) heat killed (HK) Y. pestis alone or in conjunction with Freund's complete adjuvant (FCA), cyclophosphamide (CY), BCG, or both CY and BCG. The footpad reaction elicited with 5 x 10(6) HK Y. pestis was shown to peak at 24 hr, was transferable with immune T lymphocytes but not with serum and had the classical DTH histology, The highest level of DTH occurred 6 or 8 days after immunization, according to the immunomodulator used, and immunized mice were therefore challenged with viable Y. pestis at this time. No correlation was found between DTH level and resistance of mice; only groups immunized under the potentiating effect of BCG used alone or with CY were significantly protected against Y. pestis. Control groups pretreated with BCG or BCG pretreated and immunized with a large dose of an unrelated gram negative bacterium were as susceptible to Y. pestis infection as normal mice. To promote this protective immunity, BCG and HK Y. pestis, must be injected in an area that drains to a common lymph node. No antibody to Y. pestis was found in immunized protected mice pretreated with BCG and CY and a very low antibody titre was found in immunized mice pretreated only with BCG. This serum was unable to confer resistance on recipient mice but immune cell transfer decreased the number of Y. pestis counted in the spleens of recipients 36 hr after challenge.

Animals↗

Modulation by malaria infection of the induction of T lymphocyte-dependent delayed-type hypersensitivity and antibody formation to sheep erythrocytes in mice.

A profound alteration of the inductive phase of delayed-type hypersensitivity and antibody formation to SRBC was found in malaria infected mice when sensitization with this antigen was performed intravenously at a critical time of the disease, but not after subcutaneous immunization, suggesting a major role for the spleen in the mechanism of immunodepression.

Animals↗

Immunological behavior after mycobacterial infection in selected lines of mice with high or low antibody responses.

Resistance and susceptibility to mycobacterial infection in the Biozzi high and low lines of mice which were genetically selected for their responses to heterologous erythrocytes have been found to be related to the innate ability of nonimmune macrophages to kill or inhibit the growth of the organisms during the first two weeks after infection and to their ability to mount specific and nonspecific immune responses. High antibody-producer mice were more capable of expressing cell-mediated immune parameters than low antibody-producer mice. A direct relationship was observed between the ability of bacteria (BCG vaccine) to multiply inside the reticuloendothelial system and the development of cell-mediated immunity, as measured by the delayed local reaction at the injection site, the lymphoproliferative response in the draining nodes, the tuberculin delayed-type hypersensitivity, the acquired resistance, and the adjuvant effect after BCG inoculation. In high line mice, apart from the inability of their macrophages to inhibit the early growth of bacteria, their lymphocytes in spleen and thymus were more capable of being stimulated in vitro by varying concentrations of living BCG. The data presented in this report are compatible with the hypothesis that a group of genes segregated in each line during the selective breeding controls the innate microbicidal activity.

Adjuvants, Immunologic↗

Local immune response to Mycobacterium lepraemurium in C3H and C57Bl/6 mice.

Subcutaneous footpad inoculation of living M. lepraemurium (L.MLM) induced, in high responder C57Bl/6 mice, a local granulomatous reaction associated with the production of effector cells which stopped the multiplication of bacilli in the draining popliteal node with the concurrent development of 24--48 hr delayed type hypersensitivity (DTH). The thymus-dependent local reaction did not occur after the injection of heat-killed M. lepraemurium (HK.MLM) or after the inoculation of L.MLM in nude mice. However, HK.MLM injection interfered with the onset of the local reaction and enhanced acid-fast bacteria (AFB) counts in the draining node. In low responder C3H mice, L.MLM produced a local and delayed footpad swelling but no restriction of bacilli multiplication in the draining lymph node was observed. This unresponsiveness was not due to an overloading of the inoculum dose since doses ranging from 3 x 10(4) to 3 x 10(7) MLM did not produce any granulomatous local reaction as in C57Bl/6 mice. The injection of dead bacilli in the contralateral footpad of subcutaneously (s.c.) infected C3H mice revealed Arthus-like and 18--24 hr delayed reactions. When 10(6) L.MLM per mouse were injected intravenously (i.v.), systemic infection, measured in the spleen, was found to be less restricted in C57Bl/6 than in C3H mice. Moreover, in C57Bl/6 mice low doses of L.MLM injected i.v. delayed the local reaction at first, then enhanced footpad swelling and AFB counts in the draining nodes, indicating some acquired defect of peripheral immunity. When a high dose of L.MLM (2 x 10(8)/mouse) was injected i.v., C57Bl/6 mice died sooner than C3H mice, indicating certain discrepancies between local resistance and systemic susceptibility.

Animals↗

High radiosensitivity of induction in contrast to radioresistance of expression of cells mediating delayed-type hypersensitivity during response to sheep red blood cells in mice.

The delayed-type hypersensitivity DTH) reaction observed in mice primed i.v. with low doses of sheep red blood cells was greatly decreased when mice were irradiated with 300 rad before priming. An estimation of the radiosensitivity of DTH-mediating cells (DTH-C) was performed using a titration assay after local adoptive transfer of these cells mixed with antigen into the footpad of unprimed mice. A high radiosensitivity of the induction of DTH-C was observed with a D37 of approximately 50 rad. In contrast, the expression of DTH-C appeared radioresistant, as the D37 was approximately 2000 rad.

Animals↗

Delayed-type hypersensitivity to rabies virus in mice: assay of active or passive sensitization by the footpad test.

With a purified beta-propiolactone-inactivated rabies virus, a significant increase in footpad swelling was elicited in normal or in BCG-pretreated mice after immunization with varying doses of rabies vaccine. These footpad reactions were shown to peak at 24 h and to be associated with an infiltration of newly formed blood monocytes demonstrated by histology and [125I]deoxyuridine labeling. A relationship between the lymphoproliferation and the degree of sensitization is described, and the susceptibility to cyclophosphamide treatment is also examined. Adoptive transfer of specific reactivity to normal recipient mice with immune lymphoid cells, but not with immune serum, was demonstrated, and the results represent another argument for a cell-mediated immunological mechanism.

Animals↗

Titration and circulation of cells mediating delayed type hypersensitivity in normal and cyclophosphamide treated mice during response to sheep red blood cells.

The delayed-type-hypersensitivity (DTH) reaction observed in mice primed i.v. with low doses of sheep red blood cells is not detectable after priming with large doses. Estimation of the number of DTH mediating cells (DTH-C) was performed by titration (D50 determination) using local adoptive transfer of these cells mixed with antigen into footpads of unprimed mice. In opposition to the absence of peripheral DTH-C, splenic DTH-C were more numberous after large doses than after low doses of antigen. The ability of cyclophosphamide to restore DTH responsiveness in mice primed with large doses appeared to be related to an increased cirulation of DTH-C. These cell circulated only in mice without any detectable B-cell response or in which this response was depressed. Thus a B-cell dependent splenic retention process of DTH-C is discussed as the origin of DTH unresponsiveness observed after priming with large doses of antigen.

Animals↗

Delayed type hypersensitivity in mice immunized with inactivated rabies virus.

Evidence of the DTH reaction is in agreement with in vitro observation done with the lymphoblast transformation test in rabbits (5,8) or with the cytotoxicity test in mice (7). The footpad test (FPT) fulfilled all criteria of DTH. A maximum swelling at the injection site was observed 24 h after challenge. FPT could not be transferred by immune serum. But both local and systemic transfer of dissociated spleen cells or lymph node cells sensitized recipient mice to the FPT. A lymphoproliferative response in the draining lymph node was observed after injection of RV, coinciding with the appearance of circulating cells mediating DTH and this response is not dependent upon a B-cell regulatoring mechanism (3). Evaluation of vaccines in vivo by specific DTH reaction is of interest for testing the cell-mediated immunity of these vaccines.

Adjuvants, Immunologic↗

Cytokine patterns and viral load in lymph nodes during the early stages of SIV infection.

To elucidate the initial pathogenic events in lymphoid organs, the major reservoir of virus in HIV infection, follow-up of viral load and cytokine mRNA production was performed in the rhesus macaque SIV mac251 model. In the first experiment, lymph nodes (LN) obtained from animals sacrificed at early time points following intravenous (i.v.) inoculation with a high viral dose, showed that the production of cytokine mRNA in LN (IFN gamma, IL1 beta, IL2, IL4, IL12p40, IL6, IL10, TNF alpha and TNF beta) was correlated with viral replication and persisted during the two months post-inoculation (p.i.). In the second experiment, LN were sequentially analysed in two groups of animals receiving i.v. a high or a low viral dose. The initial higher local production of IFN gamma mRNA in LN was associated with weak viraemia, the capacity of the host to decrease productive infection in LN measured at one and two months p.i., and slow disease progression.

Animals↗

Role of T lymphocytes in the resistance and immunopathology of experimental Chagas' disease. I. Histopathological studies.

The results reported here show that Trypanosoma cruzi can parasitize almost all tissues of mice; however, the T-dependent immune response controls parasite invasion, leading undesirable immunopathological effects. Inflammatory infiltrate was rare in heart or skeletal muscle and other organs of Nu/Nu, but was abundant in tissues of Nu/+ mice. Cellular inflammatory lesions could be induced in Nude mice by the transfer of lymph node cells from Nu/+ animals infected with T. cruzi.

Adrenal Glands↗