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Biomedical subjects

M Huerre

Publications and source records attributed to M Huerre.

At least 19 recordsLinked to original sources
PubMed2006

AGS3, an alpha(1-3)glucan synthase gene family member of Aspergillus fumigatus, modulates mycelium growth in the lung of experimentally infected mice.

The cell wall of human fungal pathogen Aspergillus fumigatus protects the fungus against threats from environment and interacts with the host immune system. Alpha(1-3)glucan is the major polysaccharide of Aspergillus fumigatus cell wall, and it has been shown to contribute to the virulence of diverse fungal pathogens. In A. fumigatus, three putative alpha(1-3)glucan synthase genes AGS1, AGS2 and AGS3 have been identified. AGS1 is responsible for cell wall alpha(1-3)glucan biosynthesis, but strains with deletions of either AGS1 or AGS2 are not defective in virulence [Beauvais, A., Maubon, D., Park, S., Morelle, W., Tanguy, M., Huerre, M., Perlin, D.S., Latgé, J. P., 2005. Two alpha(1-3) glucan synthases with different functions in Aspergillus fumigatus. Appl. Environ. Microbiol. 71, 1531-1538]. In contrast, we present evidence that AGS3 is also responsible for cell wall alpha(1-3)glucan biosynthesis and can modulate the virulence of A. fumigatus. An AGS3 deletion strain was found to produce faster and more robust disease than the parental strain in an experimental mouse model of aspergillosis. The apparent hyper-virulence in the AGS3-deleted mutant was correlated with an increased melanin content of the conidial cell wall, a better resistance to reactive oxygen species and a quicker germination rate. These results suggest an indirect role for AGS3 in virulence through an adaptive mechanism.

Animals↗
PubMed2005

[Disseminated histoplasmosis: an atypical ulcerous form in an HIV-infected patient].

INTRODUCTION: Histoplasma capsulatum var capsulatum is a dimorphic fungi predominating on the American continent. It is responsible for disseminated histoplasmosis associated with AIDS. The presentation in the form of cutaneous ulceration is uncommon and misleading. OBSERVATION: A 25 year-old man presented with 3 ulcerations, of 2 to 4 cm in diameter, localized on the lower lip and knees. The patient exhibited fever, alteration in his general status of health and a pulmonary interstitial syndrome. He was seropositive for the human immunodeficiency syndrome (HIV). His lymphocyte CD4+ level was of 1/mm3. Diagnosis of histoplasmosis was established by direct examination and culture of the cutaneous ulcerations and bronchoalveolar washing fluid. DISCUSSION: The clinical aspect of cutaneous localizations of disseminated histoplasmosis is usually multiple, disseminated, papular or nodular-type lesions. Ulcerations represent less than 20% of the cases described. In our patient, the aspect of the lesions at first evoked cutaneous leishmaniosis. Direct mycological examination followed by culture confirmed the final diagnosis.

Adult↗
PubMed2005

Two alpha(1-3) glucan synthases with different functions in Aspergillus fumigatus.

Alpha(1-3) glucan is a main component of the Aspergillus fumigatus cell wall. In spite of its importance, synthesis of this amorphous polymer has not been investigated to date. Two genes in A. fumigatus, AGS1 and AGS2, are highly homologous to the AGS genes of Schizosaccharomyces pombe, which encode putative alpha(1-3) glucan synthases. The predicted Ags proteins of A. fumigatus have an estimated molecular mass of 270 kDa. AGS1 and AGS2 were disrupted in A. fumigatus. Both Deltaags mutants have similar altered hyphal morphologies and reduced conidiation levels. Only Deltaags1 presented a reduction in the alpha(1-3) glucan content of the cell wall. These results showed that Ags1p and Ags2p were functionally different. The cellular localization of the two proteins was in agreement with their different functions: Ags1p was localized at the periphery of the cell in connection with the cell wall, whereas Ags2p was intracellularly located. An original experimental model of invasive aspergillosis based on mixed infection and quantitative PCR was developed to analyze the virulence of A. fumigatus mutant and wild-type strains. Using this model, it was shown that the cell wall and morphogenesis defects of Deltaags1 and Deltaags2 were not associated with a reduction in virulence in either mutant. This result showed that a 50% reduction in the content of the cell wall alpha(1-3) glucan does not play a significant role in A. fumigatus pathogenicity.

Amino Acid Sequence↗
PubMed2003

[First cases of imported cutaneous leishmaniasis in Bangui Central African Republic: efficacy of metronidazole].

Cutaneous leishmaniasis is an uncommon disease in the Central African Republic (CAR). The purpose of this report is to present a case that was imported into Bangui, CAR from the neighboring Republic of Chad. The polymorphous aspects of lesions and the spectrum of laboratory findings associated with the disease in this patient are described. Oral treatment with metronidazole led to rapid resolution with minimal scarring.

Adult↗
PubMed2003

[Cervical cancers diagnosed at the Pasteur Institute of Madagascar from 1992 to 2002].

In Madagascar, the epidemiological data actualized concerning the cancer of the collus of uterus are not available because of the absence of register of cancer. The objective of this study is to achieve a first assessment of the problem, to complete the epidemiological knowledge, to point out the tool of precoce detection of the precancerous lesions, to propose the measures aiming to improve the management of the patients and to contribute to the institution of a register of cancer. This is a retrospective survey on the frequency of the cancer of the cervix observed from 1992 to 2002 about 23,908 withdrawals addressed to the Institut Pasteur de Madagascar for anatomopathological exam and 12,605 cervical smears for cytological exam. In pathological anatomy, 2,621 (63.4%) of 4,136 cases of diagnosed cancer, have been observed in women. 687 cases (26.2%) of them were localized in the collus. The 3/4 of the cancers of the cervix is invasive and the mean age is 48.2 years old at the time of diagnosis. The cytology detects only 74 cases of invasive cancer of which most don't have an histological confirmation. 274 pre-lesions of cervix cancer were diagnosed for this period, the majority lesions are cytological diagnosis. In spite of a non representative recruitment of the general population, and by the number of withdrawals considered, these results may represent indicators of the epidemiological situation and justify the institution of program to detect the precancerous lesions in a national scale.

Academic Medical Centers↗
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↗