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Biomedical subjects

Y Carlier

Publications and source records attributed to Y Carlier.

At least 37 records · Page 2Linked to original sources
PubMed1995

Influence of maternal infection on offspring resistance towards parasites.

Immunoglobulins, parasite circulating antigens, immune cells, cytokines and other cell-related products can be transferred from infected mothers to their young. They can combine their effects to interact with the invading parasites, as well as to induce a long-term modulation of the offspring's capacity to mount an immune response to subsequent exposure to parasites. The protective effect of maternally derived antibodies may be limited by the selective transfer of immunoglobulin isotypes. Maternal antibodies may also prevent the priming of specific cells in offspring or inhibit the progeny's antibody production by interacting with B-cell receptors or with the idiotypic repertoire. The potentially beneficial priming effect of transferred parasitic antigens may be altered by the Th2-cell-biased foetal environment and such antigens may also induce deletion or anergy of T- and B-cell clones in offspring. Therefore, besides protective effects, maternal infection may downregulate the offspring's immune response. If such hyporesponsiveness may be clearly harmful (in increasing the risk or in worsening congenital or postnatally acquired infections in offspring), it can also be beneficial (in limiting the pathogenesis of some infections). Here, Yves Carlier and Carine Truyens review the rationale of these complex foeto-maternal relationships in parasitic diseases.

Journal Article↗
PubMed1995

The cachexia associated with Trypanosoma cruzi acute infection in mice is attenuated by anti-TNF-alpha, but not by anti-IL-6 or anti-IFN-gamma antibodies.

BALB/c male mice acutely infected with Trypanosoma cruzi underwent a severe weight loss (around 20%, from day 18 to 31 post-infection), when compared to age-matched uninfected animals. Though mice regained weight later, when blood parasites were hardly detectable, wasting extended over the chronic phase of infection. The onset and the magnitude of weight loss were related to the mouse susceptibility to infection, since they were respectively earlier and higher in male mice which will die than in surviving ones, in males than in females, and in BALB/c than in B6D2 [(C57B1/6 x DBA/2)F1], a mouse strain more resistant to infection. Fat weight of infected mice (male BALB/c) was reduced by 60 to 80%, whereas lean mass was unaffected and water content rose by 6 to 10% in acute and chronic infection. Haematocrit was also decreased by 15-16% in acute infection. Animals failed to compensate their energetic loss since their food intake remained similar to that of uninfected animals. Injections of neutralizing anti-TNF-alpha monoclonal antibody into infected male mice, during the first two weeks but not later in infection, significantly attenuated the weight loss. Early administration of anti-IL-6 or anti-IFN-gamma MoAbs did not improve the mouse wasting. Taken together, these data show that TNF is a key agent of cachexia occurring in the acute T. cruzi infection in mice.

Animals↗
PubMed1995

High tumor necrosis factor alpha (TNF-alpha) production in Trypanosoma cruzi-infected pregnant mice and increased TNF-alpha gene transcription in their offspring.

Since tumor necrosis factor alpha (TNF-alpha) is known to be involved in the feto-maternal relationship, this cytokine was studied in Trypanosoma cruzi-infected pregnant BALB/c mice and their fetuses and offspring. Pregnant chronically infected mice displayed significantly higher levels of circulating TNF-alpha than animals either only infected or only pregnant. TNF-alpha was undetectable in sera of uninfected and nonpregnant mice as well as in breast milk obtained from infected and uninfected animals. Fetuses from infected mice exhibited significantly more cells containing TNF-alpha mRNA in their thymus than fetuses from uninfected mothers. When infected 2 months after birth, offspring born to infected and uninfected mothers displayed similar amounts of circulating TNF-alpha during chronic infection, whereas this cytokine was only weakly detectable during the acute phase of the disease. An intravenous injection of lipopolysaccharide during acute infection strongly increased the production of TNF-alpha in offspring born to infected mothers to levels higher than those in progeny from uninfected mice. These results suggest that TNF-alpha is an important cytokine in the feto-maternal relationship during T. cruzi infection and that fetuses and offspring of infected mothers are primed to produce elevated levels of TNF-alpha.

Animals↗
PubMed1994

Trypanosoma cruzi infection in mice induces a polyisotypic hypergammaglobulinaemia and parasite-specific response involving high IgG2a concentrations and highly avid IgG1 antibodies.

Trypanosoma cruzi infection in BALB/c mice induced a reversible polyisotypic hypergammaglobulinaemia, with particularly high levels of IgG2a, IgM and IgE. Hypergammaglobulinaemia started during the acute phase of infection and persisted during chronic disease until 11-13 weeks post-infection (w.p.i.), when immunoglobulin levels, with the exception of IgE, returned near normal values. Parasite-specific antibodies counted for 14 to 23% of gammaglobulinaemia, in acute and chronic infection respectively. The titres of IgM antibodies rose from two w.p.i. IgA, IgE and IgG subclass antibodies built up gradually over the time of parasite clearance (i.e., between three and six w.p.i.). All antibody isotypes, including IgM reached significant and stable titres throughout chronic infection. IgG2a, IgG1 and IgM antibodies had constantly higher titres than the other antibody isotypes. The dominance of IgG2a antibodies was due to their high plasma concentrations, around 70% of all antibodies available in the chronic infection. IgG1 had the highest functional avidity, whereas its concentration corresponded to only 10% of the whole antibody fraction. These results indicate that T. cruzi infection in mice induces a polyisotypic humoral immune response, dominated by some antibody isotypes, with major differences in concentrations and functional avidities. This could be of crucial importance in determining the outcome of infection.

Animals↗
PubMed1994

Modulation of T-cell responsiveness during Trypanosoma cruzi infection: analysis in different lymphoid compartments.

Spleen and lymph node cells of Trypanosoma cruzi-infected mice were studied for mitogen-induced responsiveness in terms of proliferation and lymphokine production (IL-2, IFN-gamma). Splenocyte (SP) as well as lymph node cell (LN) proliferation and IL-2 production were depressed during the acute phase of the infection. Proliferative capacity of LN cells recovered completely and that of SP partially during the chronic phase. In contrast to these suppressive effects, the mitogen-induced IFN-gamma response was enhanced. In vitro co-incubation of normal SP or LN cells with trypomastigotes resulted in a reduced mitogen-induced cell proliferation and IL-2 secretion, similar to those seen with cells taken from infected mice. In contrast, trypomastigotes exerted a stimulatory activity on the mitogen-induced IFN-gamma response of both SP and LN cells. Addition of lymph node cells from T. cruzi-infected mice (LN-I) to lymph node cells of control mice (LN-C) suppressed strongly the mitogen-induced responsiveness of such cocultures. A marginal level of suppression was recorded in cocultures of spleen cells from infected mice (SP-I) and control spleen cells (SP-C). The potent suppressive cells within LN-I populations were identified as macrophage-like and such cells were absent in SP-C and peritoneal exudate cells from T. cruzi infected animals.

Acute Disease↗
PubMed1994

Interleukin-6 (IL-6) production in mice infected with Trypanosoma cruzi: effect of its paradoxical increase by anti-IL-6 monoclonal antibody treatment on infection and acute-phase and humoral immune responses.

Trypanosoma cruzi infection of mice triggered endogenous production of interleukin-6 (IL-6) during the ascending phase of parasitemia. Injections of anti-IL-6 monoclonal antibody in infected mice at the time of the serum IL-6 peak paradoxically increased IL-6 levels to 60- to 80-fold those in infected mice receiving unrelated immunoglobulins. This early and transient increase in circulating IL-6 levels modified neither the immunoglobulin nor T. cruzi-specific antibody levels of immunoglobulin G1 (IgG1), IgG2a, IgG3, IgM, IgA, and IgE isotypes or the final outcome of infection nor the blood or tissular parasite levels. However, it tended to delay mortality of mice and to increase the levels of the acute-phase protein serum amyloid P component.

Acute-Phase Reaction↗
PubMed1993

Trypanosoma cruzi upregulates nitric oxide release by IFN-gamma-preactivated macrophages, limiting cell infection independently of the respiratory burst.

The relationship between nitric oxide (N = O) produced by mouse peritoneal macrophages (MPM) and Trypanosoma cruzi infection is still poorly understood. The conditions of MPM activation by gamma-interferon (IFN-gamma) to trigger a N = O-dependent trypanocidal activity, as well as the effect of parasite infection or of reactive oxygen species (ROS) inhibitors on the N = O release were studied. T. cruzi infection occurring after a previous 24 h MPM activation induced an enhancement of nitrite levels (the stable degradation product of N = O) in cell supernatants; both the percentage of infected MPM and the number of amastigotes per infected cell were decreased in comparison to infected but non-activated MPM. Addition of superoxide dismutase or catalase to non-infected but activated MPM increased the nitrite levels; these were not detectable when L-arginine inhibitors were added together with ROS inhibitors. The latter had no effect on infection nor on nitrite levels when infection occurred after pre-activation, and induced only a weak nitrite release when infection took place before MPM activation. Altogether, these results support the involvement of N = O in the inhibition of T. cruzi infection by IFN-gamma-preactivated macrophages, together with the upregulation of N = O release by T. cruzi infection independently of the respiratory burst.

Animals↗
PubMed1993

Trypanosoma cruzi infection in mice enhances the membrane expression of low-affinity Fc receptors for IgG and the release of their soluble forms.

The membrane expression of low-affinity Fc receptors for IgG (Fc gamma RII/III) on cells and the number of Fc gamma RII/III(+) cells were studied by flow cytometry, using the 2.4G2 MoAb, in mice infected by Trypanosoma cruzi. Cells from spleen, mesenteric lymph nodes and peritoneum were collected on days 10, 20, 30 and 40 post infection (p.i.). The in vivo serum level of soluble Fc gamma RII/III, as well as its in vitro release by cells from infected mice were studied. Parasitaemia and IgG1, IgG2a and IgG2b T. cruzi-specific antibody titres were also recorded. Both the expression of Fc gamma R on cell membrane and the absolute number of Fc gamma R(+) cells increased in spleen and in mesenteric lymph nodes, but not in peritoneum. The modifications in spleen occurred in the early and late parasitaemic phase of infection, i.e., before and after detection of T. cruzi-specific antibodies (from day 10 to 40 p.i.). In mesenteric lymph nodes, the variations were observed only in the early acute infection, when antibodies were not yet detectable at significant levels (on days 10 and 20 p.i.). Higher levels of soluble Fc gamma R were detected in sera and in culture supernatants of spleen and lymph node cells from day 20 to 40 p.i. These results show that T. cruzi infection in mice upregulates the expression and the release of Fc gamma RII/III, in the acute phase of infection, before as well as after the rise of antibody response.

Animals↗
PubMed1993

An Fc gamma RII-, Fc gamma RIII-specific monoclonal antibody (2.4G2) decreases acute Trypanosoma cruzi infection in mice.

In order to study the role of Fc gamma Rs in Trypanosoma cruzi infection in mice, the 2.4G2 monoclonal antibody (MAb), specific to the extracellular domains of Fc gamma RII and Fc gamma RIII, was injected intraperitoneally into mice. Flow cytometry studies of uninfected mice showed that 2.4G2 MAb bound to peritoneal and lymph node cells, respectively, on days 2 and 6 after injection. Repeating 2.4G2 injections every 3 to 4 days decreased the availability of Fc gamma Rs on peritoneal, lymph node, and spleen cells. Injections of 2.4G2 MAb into T. cruzi-infected mice, at days -1, 3, 7, 11, 16, 20, and 24 relative to infection, reduced mortality in comparison with that in infected animals injected with an unrelated MAb (50 versus 93.3% mortality; P < 0.01). Parasitemia in 2.4G2-treated mice was significantly (three times) lower than in control animals on days 21 and 24 postinfection (P < 0.05), before parasite-specific antibodies were detectable at significant levels. Immunoglobulin and T. cruzi-specific antibody levels were similar in all groups of mice. These results indicate that repeated injections of 2.4G2 MAb administered to acutely infected mice reduce the in vivo infection level, suggesting that Fc gamma Rs play a role in the early host invasion by T. cruzi parasites.

Acute Disease↗
PubMed1992

Trypanosoma cruzi: enhanced alpha-macroglobulin levels correlate with the resistance of BALB/cj mice to acute infection.

Trypanosoma cruzi proteinases are very likely involved in host-cell invasion. Physiological plasma-proteinase inhibitors from the macroglobulin (MG) family, among them alpha-2-macroglobulin (A2M), are found in tissues and in the plasma of mammals. By complexing to all classes of proteinases, MGs inhibit their action on high-molecular-weight substrates. In vitro studies have shown that A2M impairs T. cruzi proteases and, consequently, the parasite's ability to invade host cells and enhances the phagocytic and microbicidal actions of resident macrophages against T. cruzi. To test the hypothesis of a putative "protective" effect for MG, we quantified it in BALB/cj mice during the course of an experimental T. cruzi infection, comparing a posteriori the levels in mice that died with those in animals that survived, which were considered as being susceptible and resistant to the infection, respectively. The results showed that surviving mice showed an increase in plasma concentrations of MG during the first few weeks after the infection, whereas the levels in mice that died during the acute phase did not differ significantly from those in non-infected mice. These findings and the previous in vitro data indicate a role for physiological proteinase inhibitors, particularly alpha-macroglobulins, in resistance to T. cruzi infection, whereby a balance between parasite proteases and host protease inhibitors may be crucial. MG may thus participate in the complex network of reactions involved in the early acute phase of the disease and contribute by conferring to the host an ability to survive the infection.

Acute Disease↗
PubMed1992

Chagas' disease: decreased resistance to Trypanosoma cruzi acquired infection in offspring of infected mice.

The course of Trypanosoma cruzi infection was studied in an experimental model, using the offspring of mice that were chronically infected with T. cruzi. When infected two months after birth, a higher mortality rate in heavily parasitized mice occurred in these offspring than in controls born to uninfected mothers. The harmful maternal influence reached a maximum when offspring were exposed both to prenatal (placental) and postnatal (lactating) influences. It was a reversible phenomenon that led to a T. cruzi-specific failure of the offspring to control the acute phase of the infection. Such features are suggestive of a maternally-induced impairment of the immune response of the offspring.

Analysis of Variance↗
PubMed1992

Direct identification of Trypanosoma cruzi natural clones in vectors and mammalian hosts by polymerase chain reaction amplification.

The polymerase chain reaction was used to amplify the highly variable region of the kinetoplast minicircle of Trypanosoma cruzi directly in biological samples (feces of infected Triatomine bugs, blood samples of experimentally infected mice, and artificially infected human blood samples). Hybridization of the amplified DNAs with reference stocks representing different genotypes (natural clones) enabled us to characterize the stocks infecting the biological samples under study. The main interest of this new approach is the diagnosis of T. cruzi infection and simultaneous direct identification of the different natural clones circulating in vectors and mammalian blood without isolation of the stocks. The suitability of this technique for epidemiologic studies is also discussed.

Animals↗
PubMed1991

Endogenous IFN-gamma is required for resistance to acute Trypanosoma cruzi infection in mice.

In order to study the role of endogenous IFN-gamma in Trypanosoma cruzi infection in mice, a potent murine IFN-gamma-specific mAb was injected i.p. on days -1, 7, and 14, relative to infection. Irrespective of the parasite inocula (100 or 25,000), groups of antibody-treated mice had significantly greater cumulative mortality rates than did appropriate controls. In antibody-treated mice, mean survival times were also significantly shorter, and maximum mean parasitemia levels were significantly higher, than in controls. Moreover, the number of amastigote nests in tissues was higher than in control mice and attained a maximum at the same time as parasitemia. As evident from kinetic studies of neutralizing activity, injected mAb were rapidly consumed in infected, but not in noninfected, mice, which is suggestive of massive IFN-gamma production during the early parasitemic phase of the disease. Nevertheless, IFN-gamma remained undetectable in the sera of infected but untreated mice. Unexpectedly, however, a peak of IFN-like antiviral activity, characterizable as a mixture of IFN-gamma and IFN-beta, appeared in mAb-treated mice that survived to infection at a time when neutralizing activity of injected mAb had drastically decreased in the circulation. We hypothesize that this high level of artificially induced endogenous IFN-gamma, not neutralized by the amounts of injected mAb, was due to the more intense parasite multiplication occurring in mAb-treated mice, which in turn may have induced an increased amount of various cytokines. TNF-alpha was not found in the serum of our mice. The humoral immune response entered its exponential phase at a time point later than that when protection by endogenous IFN-gamma was evident. Treatment with IFN-gamma-specific antibody, as applied in our study, failed to affect the level of different Ig isotypes or of T. cruzi-specific antibodies. Our study clearly indicates that IFN-gamma is produced early in acute T. cruzi infection and exerts a protective effect that is probably independent from the humoral immune response.

Acute Disease↗
PubMed1991

Trypanosoma cruzi but not Trypanosoma brucei fails to induce a chemiluminescent signal in a macrophage hybridoma cell line.

Macrophage-Trypanosoma cruzi interactions were studied by using a newly generated macrophage hybridoma cell line (2C11-12) that was selected for its capacity to produce high levels of reactive oxygen intermediates. This cell line was found to be a suitable host cell for T. cruzi, and intracellular parasitic development could be inhibited by activation with gamma interferon. When exposed to opsonized Trypanosoma brucei, Micrococcus lysodeikticus, or Legionella pneumophila, the activated macrophage cell line produces a high chemiluminescent signal, indicating the release of reactive oxygen intermediates. Alternatively, when opsonized T. cruzi was added to these activated macrophages, this parasite failed to stimulate a chemiluminescent response, suggesting an impairment in the triggering of the respiratory burst.

Animals↗
PubMed1991

[Chronic asymptomatic hypereosinophilia. Apropos of a case of occupational toxocariasis].

The authors observed a case of asymptomatic toxocariasis in a lady aged 60, engaged in dog-breeding since twenty years. The various causes of hypereosinophilia are discussed. The epidemiology of Toxocariasis and the essential role of serologic tests--in particular ELISA detection of a larval antigen--are recalled. In this particular case, therapeutic abstention is justified.

Animals↗
PubMed1987

Pregnancy and humoral immune response in mice chronically infected by Trypanosoma cruzi.

The effect of pregnancy on the humoral immune response induced by Trypanosoma cruzi was studied in groups of chronically infected and pregnant mice (IP) or chronically infected and nonpregnant mice (INP) of strain BALB/c. Groups of noninfected and nonpregnant mice (NINP) or noninfected and pregnant mice (NIP) served as controls. The pregnant mice were killed on day 17 of pregnancy. Anti-T. cruzi immunoglobulin G (IgG) and IgM antibodies, detected by immunofluorescence or enzyme-linked immunosorbent assay or both, underwent a pregnancy-associated decrease of 20 to 40%, whereas complement-mediated lytic antibodies were unaffected by pregnancy. Immunoblotting analysis indicated identical specificities of the anti-T. cruzi antibodies in IP and INP groups. The levels of all the immunoglobulin isotypes (particularly IgG2a and IgG3), circulating immune complexes, rheumatoid-like factor, and anti-DNA antibodies were considerably increased during chronic infection (NINP versus INP), which could be related to the high degree of polyclonal B-cell activation occurring in T. cruzi infection. However, pregnancy significantly decreased (by 20 to 60%) such parameters. IgG levels were particularly affected (by 40 to 60%), and the decreases could be ordered as follows: IgG3 greater than IgG2a greater than IgG1 greater than IgG2b for IP versus INP. Comparisons between the noninfected groups indicated differences only in IgG levels. These results indicate the following. (i) The specific humoral anti-T. cruzi immune response is weakly affected by pregnancy, which is not sufficient to modify the course of the mother's infection. (ii) Pregnancy does not modify the expression of the anti-T. cruzi antibody repertory. (iii) Pregnancy reduces the polyclonal B-cell activation, particularly the levels of the IgG isotypes undergoing the greatest activation.

Animals↗
PubMed1987

Interactions between chronic murine Trypanosoma cruzi infection and pregnancy: fetal growth retardation.

Fetal growth, reproductive capacity, and parasitemia were studied in three groups of BALB/c mice: pregnant and chronically infected with Trypanosoma cruzi, non-pregnant but similarly infected, and pregnant but noninfected. The pregnant mice were killed on day 17 of pregnancy. Comparisons of the two pregnant groups showed significant differences in fetal weights and x18 magnified ossification lengths of radius and cubitus, whereas placental weights were not modified. The results indicate that intrauterine growth retardation occurs during chronic murine T. cruzi infection. No difference was noted between the reproductive capacities of the two pregnant groups. Parasitemias were similar in infected pregnant and control groups. Mice of all groups survived infection until killing. Pregnancy, therefore, does not influence chronic murine T. cruzi infection. Parasites were never found in fetal blood, indicating a very low, if any, frequency of transplacental transmission of parasite during the chronic phase of infection.

Animals↗