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Biomedical subjects

M Huerre

Publications and source records attributed to M Huerre.

At least 19 recordsLinked to original sources
PubMed2002

Temporary restoration of immune response against Toxoplasma gondii in HIV-infected individuals after HAART, as studied in the hu-PBMC-SCID mouse model.

We studied immune reconstitution against the parasite T. gondii in HIV-infected patients treated for 1 years with highly active antiretroviral therapy (HAART). We used SCID mice, humanized with peripheral blood mononuclear cells (PBMC) from patients, which were then infected with T. gondii cysts. Mice humanized with PBMC from patients before the start of HAART were highly susceptible to infection. In contrast, mice humanized with PBMC from patients who had received HAART for 6 months displayed higher survival rates, correlating with lower intracerebral parasite loads. However, this resistance was lost during follow up because mice humanized with PBMC from patients treated with HAART for 12 months survived for no longer than mice that had not been humanized. Specific lymphocyte proliferation assays showed that the increase in proliferative response depended on treatment duration and that HAART induced changes in IFN-gamma secretion in the presence of Toxoplasma antigens. Thus, our results indicate partial immune reconstitution against T. gondii in HIV-infected patients following HAART, possibly due to changes in the patterns of specific IFN-gamma production and redistribution of functional memory CD4+ cells.

Animals↗
PubMed2001

Changes in AIDS-related lymphoma since the era of highly active antiretroviral therapy.

HIV infection is associated with a high incidence of AIDS-related lymphomas (ARLs). Since the use of highly active antiretroviral therapy (HAART), the incidence of AIDS-defining illnesses has decreased, leading to a significant improvement in survival of HIV-infected patients. The consequences of HAART use on ARL are under debate. This study compared the incidence and the characteristics of ARL before and after the use of HAART in a large population of HIV-infected patients in the French Hospital Database on HIV (FHDH) and particularly in 3 centers including 145 patients with proven lymphoma. Within the FHDH, the incidence of systemic ARL has decreased between 1993-1994 and 1997-1998, from 86.0 per 10 000 to 42.9 per 10 000 person-years (P < 10(-30)). The incidence of primary brain lymphoma has also fallen dramatically between the periods, from 27.8 per 10 000 to 9.7 per 10 000 person-years (P < 10(-11)). The analysis of 145 cases of ARL in 3 hospitals showed that known HIV history was longer in the second period than in the first period among patients with systemic ARL (98 versus 75 months; P <.01). Patients had a higher number of CD4 cells at diagnosis during the second period (191 versus 63/microL, P = 10(-3)). Survival of patients with systemic ARL also increased between the periods (from 6 to 20 months; P =.004). Therefore, the profile of ARL has changed since the era of HAART, with a lower incidence of systemic and brain ARL. The prognosis of systemic ARL has improved.

Antiretroviral Therapy, Highly Active↗
PubMed2001

A transgenic model for listeriosis: role of internalin in crossing the intestinal barrier.

Listeria monocytogenes is responsible for severe food-borne infections, but the mechanisms by which bacteria cross the intestinal barrier are unknown. Listeria monocytogenes expresses a surface protein, internalin, that interacts with a host receptor, E-cadherin, to promote entry into human epithelial cells. Murine E-cadherin, in contrast to guinea pig E-cadherin, does not interact with internalin, excluding the mouse as a model for addressing internalin function in vivo. In guinea pigs and transgenic mice expressing human E-cadherin, internalin was found to mediate invasion of enterocytes and crossing of the intestinal barrier. These results illustrate how relevant animal models for human infections can be generated.

Animals↗
PubMed2001

Capacity of mouse mast cells to prime T cells and to induce specific antibody responses in vivo.

Mouse, human and rat mast cells have been shown to express major histocompatibility complex II molecules and present antigens to specific T-cell hybridomas in vitro. The purpose of our investigation was to determine whether mouse mast cells are able to initiate specific immune responses in vivo. Induction of anti-dinitrophenyl (DNP) immunoglobulin G1 (IgG1) and IgG2a antibodies was performed by transferring ovalbumin (OVA)-DNP-pulsed bone marrow-derived mast cells (BMMC), B cells, or macrophages into naive mice which were boosted later with soluble antigen. Cultured spleen cells from immunized mice were tested for their cytokine content. Our data show that mast cells were by far better inducers of anti-DNP IgG1 antibodies than were B cells and macrophages. In contrast, anti-DNP IgG2a response induced by macrophages was much stronger than that obtained with mast cells whereas B cells were completely unable to elicit this response. In addition to a high index of cell proliferation, spleen cells from mast cell-injected mice produced more interferon-gamma than those mice who received macrophages or B cells by two- to fivefold, and almost 10-fold, respectively. Mast cell-deficient Wf/Wf mice were compared with their normal +/+ littermates and with mast cell-reconstituted Wf/Wf mice to develop delayed-type hypersensitivity (DTH) reactions as well as humoral immune responses. Mast cell sufficient mice as well as mast cell-reconstituted Wf/Wf mice developed significantly increased DTH reactions (P = 0.02, and 0.03, respectively) and higher anti-OVA-specific antibody responses as compared with Wf/Wf mice. Our data suggest that mast cells have the potential to up-regulate both humoral and cellular immune responses in vivo.

Animals↗
PubMed2001

Variations in biological features of West Nile viruses.

Pathological findings in humans, horses, and birds with West Nile (WN) encephalitis show neuronal degeneration and necrosis in the central nervous system (CNS), with diffuse inflammation. The mechanisms of WN viral penetration of the CNS and pathophysiology of the encephalitis remain largely unknown. Since 1996, several epizootics involving hundreds of humans, horses, and thousands of wild and domestic bird cases of encephalitis and mortality have been reported in Europe, North Africa, the Middle East, Russia, and the USA (see specific chapters in this issue). However, biological and molecular markers of virus virulence should be characterized to assess whether novel strains with increased virulence are responsible for this recent proliferation of outbreaks.

Aedes↗
PubMed2001

Genetic evidence for an interferon-antagonistic function of rift valley fever virus nonstructural protein NSs.

Rift Valley fever virus (RVFV), a phlebovirus of the family Bunyaviridae, is a major public health threat in Egypt and sub-Saharan Africa. The viral and host cellular factors that contribute to RVFV virulence and pathogenicity are still poorly understood. All pathogenic RVFV strains direct the synthesis of a nonstructural phosphoprotein (NSs) that is encoded by the smallest (S) segment of the tripartite genome and has an undefined accessory function. In this report, we show that MP12 and clone 13, two attenuated RVFV strains with mutations in the NSs gene, were highly virulent in IFNAR(-/-) mice lacking the alpha/beta interferon (IFN-alpha/beta) receptor but remained attenuated in IFN-gamma receptor-deficient mice. Both attenuated strains proved to be excellent inducers of early IFN-alpha/beta production. In contrast, the virulent strain ZH548 failed to induce detectable amounts of IFN-alpha/beta and replicated extensively in both IFN-competent and IFN-deficient mice. Clone 13 has a defective NSs gene with a large in-frame deletion. This defect in the NSs gene results in expression of a truncated protein which is rapidly degraded. To investigate whether the presence of the wild-type NSs gene correlated with inhibition of IFN-alpha/beta production, we infected susceptible IFNAR(-/-) mice with S gene reassortant viruses. When the S segment of ZH548 was replaced by that of clone 13, the resulting reassortants became strong IFN inducers. When the defective S segment of clone 13 was exchanged with the wild-type S segment of ZH548, the reassortant virus lost the capacity to stimulate IFN-alpha/beta production. These results demonstrate that the ability of RVFV to inhibit IFN-alpha/beta production correlates with viral virulence and suggest that the accessory protein NSs is an IFN antagonist.

Animals↗
PubMed2001

Cytotoxic T cells in AIDS colonic cryptosporidiosis.

BACKGROUND/AIMS: It is not known how enteric cryptosporidiosis induces severe intestinal impairment despite minimal invasion by the parasite. The aim of this study was to analyse the histological features and locally implicated immune cells in colonic biopsies of AIDS related cryptosporidiosis. PATIENTS/METHODS: Colonic biopsies from patients with AIDS related cryptosporidiosis (n = 10, group I), patients with AIDS but without intestinal infection (n = 9, group II), and human seronegative controls (n = 9, group III) were studied. Using immunohistochemistry the infiltrating mononuclear cells were analysed in both the epithelium and lamina propria for the expression of CD3, CD8, TiA1, granzyme B, and CD68 and for glandular expression of human major histocompatibility complex DR antigen (HLA-DR). RESULTS: Severe histological changes, resulting in abundant crypt epithelial apoptosis and inflammatory infiltrate in the lamina propria, were seen in all biopsies from group I. A significant increase of CD8+, TiA1+, and granzyme B+ T cells in the lamina propria and HLA-DR glandular expression was noted in group I compared with groups II and III. However, the number of intraepithelial lymphocytes, lamina propria CD3+ T cells, and macrophages was not significantly increased in cryptosporidiosis specimens compared with controls. CONCLUSION: Epithelial apoptosis mediated by granzyme B+ cytotoxic host T cells might play a major role in the development of colonic lesions in AIDS related cryptosporidiosis.

AIDS-Related Opportunistic Infections↗
PubMed2001

[Infiltrated cutaneous leishmaniasis and sporotrichosis caused by Leishmania major. First Senegalese case].

We report in Senegal a case of infiltrated cutaneous leishmaniasis and sporothricoid due to Leishmania major MON-74. The diagnosis of our case was based on the cytologic, histologic and immunoparasitological examination. The patient was completely cured by 3 courses of 15 days of glucan-time. Our case completes the spectrum of the clinical presentation of tegumentary leishmaniasis.

Adult↗
PubMed2001

Blockade of CD14 aggravates experimental shigellosis.

Shigella infections lead to severe inflammation associated with destruction of colonic mucosa. We assessed the effect of in vivo blockade of CD14 on the outcome of experimental Shigella infection in rabbits. A total of 17 rabbits were divided into two groups: 8 received a single i.v. dose of anti-rabbit CD14 monoclonal antibody prior to infection with an invasive Shigella flexneri strain; the remainder served as controls. The anti-CD14-treated rabbits exhibited more severe tissue destruction and a 50-fold increase in bacterial invasion of the intestinal mucosa when compared to controls. Similar numbers of polymorphonuclear leukocytes were recruited to the intestinal mucosa in both groups despite the massive bacterial invasion seen in the CD14-blocked group. No statistically significant differences were seen in levels of IL-1beta nor in the ratio of IL-1RA/IL-1beta for either group. In contrast, higher quantities of TNF-alpha were observed in the CD14-blocked group. To conclude, anti-CD14 treatment had a detrimental effect on the capacity of Shigella-infected animals to clear the infection.

Animals↗
PubMed2001

[Diagnostic pitfalls in infectious disease pathology].

Numerous images observed in histopathology and cytopathology can mimic pathogens such as mycotic agents, parasites (protozoa or helminthes), bacteria or virus. An error of diagnosis may provoke the administration of a non efficient treatment which can also be toxic. The present review describes these false pathogens which can correspond to exogenous or endogenous agents. Basic morphological analysis of mycotic agents, parasites, bacteria and cytopathogenic viral effects are successively presented. Then, the main diagnostic pitfalls which can be observed during these infections are exposed. Finally, diagnostic problems occurring in case of contamination are rapidly cited.

Bacterial Infections↗
PubMed2001

[Colonic actinomycosis. Clinical, endoscopic and histological aspects in one patient].

Colonic location of actinomycosis must be distinguished from infected colonic carcinoma and other colonic inflammatory pseudotumors. The diagnosis is often made by histological examination of the tumor. Initial treatment consists in surgery, followed by an antibiotic treatment. We report the case of a 32-year old woman with a right colonic actinomycosis.

Actinomycosis↗
PubMed2000

Blockade of CD14 increases Shigella-mediated invasion and tissue destruction.

Shigella is a diarrheal pathogen that causes disease through invasion of the large intestinal mucosa. The endotoxin of the invading bacterium may play a key role in the disease process by causing inflammation and tissue injury during infection. Earlier studies have shown that various animal species lacking functional CD14 were protected against endotoxin-mediated shock. Rabbits experimentally infected with Shigella were used to test the hypothesis that blockade of endotoxin-induced cell activation with anti-CD14 mAb would diminish inflammation and thus disease severity. Unexpectedly, we observed that the intestinal mucosa of anti-CD14-treated animals exhibited a 50-fold increase in bacterial invasion and more severe tissue injury compared with controls. Despite higher bacterial loads in treated animals, the numbers of polymorphonuclear leukocytes that were recruited to the infection site were similar to those in controls. Furthermore, the phagocytic cells of CD14-blocked animals produced IL-1 and TNF-alpha. Moreover, in vitro blockade of CD14 did not impede bactericidal activity. Thus, anti-CD14 treatment interfered with host defense mechanisms involved with removal/eradication of Shigella.

Animals↗
PubMed2000

Detection and genetic polymorphism of human herpes virus type 8 in endemic or epidemic Kaposi's sarcoma from West and Central Africa, and South America.

Kaposi's-sarcoma-associated herpesvirus(KSHV)/human-herpes-virus-8(HHV-8) sequences originally detected in AIDS-associated Kaposi's sarcoma have been found in almost every KS tested, whether endemic, classic, iatrogenic or epidemic. Most of the studies on African KS involved East African patients. We report herewith the study of 17 African or Guyanan KS patients, 3 with epidemic KS (EKS) from Central African Republic, 3 from Senegal (2 EKS and 1 endemic KS), 3 EKS from Cameroon and 8 from French Guiana (3 EKS and 5 endemic KS). Serum-specific antibodies directed against latent and/or lytic HHV-8 antigens were present in 16 of them (94%), detected either by immunofluorescence assay and/or by immunoperoxidase. Polymerase chain reaction (PCR), using specific primers for HHV-8 ORF26 (233 bp) and ORF75 (601 bp), was carried out on DNA extracted from KS cutaneous biopsies, clinically uninvolved skin biopsies and peripheral-blood mononuclear cells (PBMC). HHV-8 DNA was detected in 16 out of 16 (100%) KS biopsies, regardless of their origin or clinico-pathological sub-type, in 7 out of 15 (47%) normal skin samples and 7 out of 16 (44%) PBMC. Comparative PCR, carried out in 7 patients, regularly found a much higher viral load in KS biopsies than in autologous normal skin and PBMC samples. Sequencing of fragments of the ORF26 and of the ORF75 demonstrated that the 16 HHV-8 strains were of the A, B or C sub-type. Furthermore, sequences of the entire ORF K1 of 4 strains showed that these HHV-8 strains of African origin were of the A5 or the B sub-type.

AIDS-Related Opportunistic Infections↗
PubMed2000

Negative regulation of autoreactive B cells in transgenic mice expressing a human pathogenic cold agglutinin.

Cold agglutinins (CA) are autoantibodies that bind to erythrocyte carbohydrates at low temperatures and induce complement-mediated cell lysis, thus causing hemolytic anemia. Tolerance mechanisms towards CA-expressing B cells and the factors inducing pathogenic CA production are unknown. In order to develop an animal model for CA disease, we have produced transgenic mice expressing the heavy or the light chain of a human CA, previously shown to be pathogenic to the mouse. Expression of the human H chain alone resulted in a B cell maturation block at the pro-B stage, and did not induce allelic exclusion. In double-transgenic mice, co-expression of the human H and L chains restored B cell development but the majority of bone marrow cells expressing the human IgM were eliminated by deletion. In the periphery, B cells were depleted, and a large proportion of the remaining cells co-expressed a human and a murine H chain, secreting "mixed" IgM. A few autoreactive cells, predominating in the peritoneal cavity, escaped tolerance mechanisms and secreted transgenic IgM. The autoreactive B cells are amenable to polyclonal stimulation, making these transgenic mice a suitable model for a human autoimmune disease.

Agglutinins↗
PubMed2000

Hyperexpression of ICAM-1 and CD36 in placentas infected with Plasmodium falciparum: a possible role of these molecules in sequestration of infected red blood cells in placentas.

AIMS: During pregnancy, Plasmodium falciparum malaria is frequent and associated with maternofetal complications. This could be the consequence of sequestration by several adhesion molecules of parasite-infected red blood cells in syncytiotrophoblast. To investigate the expression of ICAM-1 and CD36, two of the adhesion molecules for Plasmodium falciparum, an immunohistochemical study was carried out in malaria-infected placentas. METHODS AND RESULTS: Thirty-five infected and 35 noninfected samples were chosen randomly. According to the histological classification of Bulmer, the infected placentas were separated in three groups: active, active chronic and past-chronic infection. CD36 was localized in the cytoplasm of stromal cells of terminal villi of infected or noninfected placentas, but not in syncytiotrophoblast. ICAM-1 was detected in the cytoplasm of stromal and endothelial villous cells in both infected and noninfected placentas and in syncytiotrophoblast of eight infected placentas showing more frequently active than active chronic or past-chronic infection (P < 0.001). The percentage of cells immunostained for CD36 or ICAM-1 was evaluated in the terminal villi. The proportion of villous cells, with ICAM-1 and CD36 immunostaining, was significantly higher in infected vs. noninfected placentas (P < 0.0001) and CD36 was detected more in acute inflammatory vs. past-chronic inflammatory placentas (P < 0.05). CONCLUSIONS: The higher expression of ICAM-1 in infected placentas and its localization in syncytiotrophoblast particularly during acute infection, suggest ICAM-1 can act directly in the sequestration of parasite-infected red blood cells (IRBCs). On the other hand, the expression of CD36 is influenced by the presence of IRBCs without being directly implicated in sequestration of IRBCs. The hyperexpression of these two molecules could explain the high frequency of malaria during pregnancy.

Adult↗
PubMed2000

Macrophage subsets harbouring Leishmania donovani in spleens of infected BALB/c mice: localization and characterization.

The purpose of the current study was to characterize parasite-containing cells located in spleens of BALB/c mice infected with Leishmania donovani. In particular, expression of MHC class II molecules by these cells was examined to determine whether they could potentially act as cells capable of immunostimulating Leishmania-reactive CD4+ T lymphocytes. To this end, an immunohistological analysis of spleens taken at various time points after infection was undertaken. Using this approach, we observed, in the red pulp, the formation of small cellular infliltrates containing heavily infected macrophages that could be stained with the monoclonal antibodies MOMA-2 and FA/11. All of them expressed high levels of MHC class II molecules. Parasites were also detected in the white pulp, especially in MOMA-2+, FA/11+ and MHC class II+ macrophages of the periarteriolar lymphocyte sheath and in MOMA-2+ marginal zone macrophages. Infected cells were further characterized by fluorescence microscopy after their enrichment by adherence. All infected mononuclear cells recovered by this procedure could be stained with MOMA-2 and FA/11 and thus very probably belonged to the mononuclear phagocyte lineage. Furthermore, all of them strongly expressed both MHC class II as well as H-2M molecules, regardless of the time points after infection. Analysis of the parasitophorous vacuoles (PV) by confocal microscopy showed that these compartments were surrounded by a membrane enriched in lysosomal glycoproteins lamp-1 and lamp-2, in macrosialin (a membrane protein of prelysosomes recognized by FA/11) and in MOMA-2 antigen. About 80% of the PV also had MHC class II and H-2M molecules on their membrane. Altogether, these data indicate that in the spleens of L. donovani-infected mice, a high percentage of amastigotes are located in macrophages expressing MHC class II molecules and that they live in PV exhibiting properties similar to those of PV detected in mouse bone marrow-derived macrophages exposed to a low dose of interferon gamma (IFN-gamma) and infected in vitro.

Animals↗
PubMed2000

Effect of Chlamydia trachomatis infection and subsequent tumor necrosis factor alpha secretion on apoptosis in the murine genital tract.

The pathology observed during Chlamydia infection is due initially to localized tissue damage caused by the infection itself, followed by deleterious host inflammatory responses that lead to permanent scarring. We have recently reported that the infection by Chlamydia in vitro results in apoptosis of epithelial cells and macrophages and that infected monocytes secrete the proinflammatory cytokine interleukin-1beta. At the same time, proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) can also trigger apoptosis of susceptible cells. To study the possible relationship between Chlamydia trachomatis infection and apoptosis in vivo, we used the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling technique to determine whether infection may cause apoptosis in the genital tract of mice and, conversely, whether cytokines produced during the inflammatory response may modulate the level of apoptosis. Our results demonstrate that infected cells in the endocervix at day 2 or 7 after infection are sometimes apoptotic, although there was not a statistically significant change in the number of apoptotic cells in the endocervix. However, large clumps of apoptotic infected cells were observed in the lumen, suggesting that apoptotic cells may be shed from the endocervix. Moreover, there was a large increase in the number of apoptotic cells in the uterine horns and oviducts after 2 or 7 days of infection, which was accompanied by obvious signs of upper tract pathology. Interestingly, depletion of TNF-alpha led to a decrease in the level of apoptosis in the uterine horns and oviducts of animals infected for 7 days, suggesting that the inflammatory cytokines may exert part of their pathological effect via apoptosis in infected tissues.

Animals↗