Micheline Lagranderie - Academia.edu (original) (raw)

Papers by Micheline Lagranderie

Tubercle and Lung Disease, 1994

Journal of Bacteriology

Functional domains of pAL5000 were determined by gene disruption and deletion analysis. Of the fi... more Functional domains of pAL5000 were determined by gene disruption and deletion analysis. Of the five plasmid open reading frames (ORFs), ORF1 to ORF5, and a putative origin of replication previously identified (J. Rauzier, J. Moniz-Pereira, and B. Gicquel-Sanzey, Gene 71:315-321), two of the ORFs (ORF3 and ORF4) were deemed dispensable for plasmid replication. A "mini" mycobacterium-Escherichia coli shuttle plasmid applicable for general recombinant DNA studies in mycobacteria was constructed by using the gene for Kanr (Tn903) as a selective marker. Heterologous expression of the gene for Kanr was confirmed by Western blotting (immunoblotting) analysis.

Infection and Immunity

New vaccines against tuberculosis are urgently required because of the impressive incidence of th... more New vaccines against tuberculosis are urgently required because of the impressive incidence of this disease worldwide and the highly variable protective efficacy of the current vaccine. The possibility of creating new live vaccines by the rational attenuation of strains from the Mycobacterium tuberculosis complex was investigated. Two auxotrophic mutants of M. tuberculosis and M. bovis BCG were constructed by disruption of one of their purine biosynthetic genes. These mutants appeared unable to multiply in vitro within mouse bone-marrow derived macrophages. They were also attenuated in vivo in the mouse and guinea pig animal models. In guinea pigs, the two mutants induced strong delayed-type hypersensitivity response to purified protein derivative. In a preliminary experiment, the two mutants were compared to the BCG vaccine for their protective efficacy in a challenge against aerosolized virulent M. tuberculosis in the guinea pig model. Both mutants conferred some level of protecti...

Revue des Maladies Respiratoires

Introduction Influenza is a highly contagious acute respiratory disease that causes considerable ... more Introduction Influenza is a highly contagious acute respiratory disease that causes considerable mortality every year. The etiological agent is the ssRNA influenza A virus (LAV). IAV is a major health challenge due to antigenic variation and animal reservoirs. Although vaccines and antiviral substances to control influenza have been developed, these treatments are not available Worldwide and their efficacy is not optimal. Therefore, research work on the pathogenesis of influenza infection and analysis of host immune response against the virus are still needed. Recently, we demonstrated that the innate immunity receptor TLR3 and its signaling-associated molecule TRIF play a key role in the immune response of respiratory epithelial cells to IAV (J Biol Chem 2005 ; 280 : 5571). Here, we evaluated the role of TLR3 in influenza-mediated acute pneumonia using an experimental animal model. Methods Wild-type and TLR3-/- mice were infected by 300 pfu influenza A/Scotland/20/74(H3N2) virus an...

Expert review of clinical immunology, 2014

Clinical evidence indicates that Bacillus Calmette-Guérin (BCG) vaccination exerts anti-inflammat... more Clinical evidence indicates that Bacillus Calmette-Guérin (BCG) vaccination exerts anti-inflammatory effects in diseases such as asthma, multiple sclerosis or Type 1 diabetes. Although the exact mechanisms for this activity remain debated, the capacity of mycobacteria to induce regulatory T cells (Tregs) in vivo has been widely reported. However, adverse events associated with live BCG prevent its repeated use, especially in immunocompromised individuals. This article reviews the preclinical data showing a potent, systemic and long-term anti-inflammatory effect in animal models of allergic asthma, inflammatory bowel disease and atherosclerosis with a preparation of BCG inactivated by Extended Freeze-Drying (EFD BCG). It also presents the characteristics of EFD BCG-induced Tregs which play a crucial role in the immunomodulation of various inflammatory diseases. Finally, it compares EFD BCG with other approaches based on the therapeutic use of Tregs in humans.

Vaccine, Jan 18, 2000

After oral or intragastric administration of BCG to mice, comparable numbers of IFN gamma and TNF... more After oral or intragastric administration of BCG to mice, comparable numbers of IFN gamma and TNF gamma producing cells were detected in both local (Peyer's patches) and central (spleen) lymphoid organs. Similar levels of precursors of CD8+ cytotoxic T lymphocytes specific for mycobacterial antigens were also found in the spleen and the mesenteric lymph nodes. These immune responses remained high over the course of 3 months, the duration of observation. Oral administration of BCG led to an enlargement of the cervical lymph nodes, which contained high levels of viable bacteria. In contrast, no adverse effects were observed in mice given the BCG via the intragastric route. These two routes of immunization induced similar levels of protective immunity to those observed in mice immunized via the subcutaneous route against a challenge with a virulent Mycobacterium tuberculosis strain (H37Rv).

Infection and immunity, 1997

Recombinant Mycobacterium bovis BCG expressing foreign antigens represents a promising candidate ... more Recombinant Mycobacterium bovis BCG expressing foreign antigens represents a promising candidate for the development of future vaccines and was shown in several experimental models to induce protective immunity against bacterial or parasitic infections. Innate resistance to BCG infection is under genetic control and could modify the immune responses induced against an antigen delivered by such engineered microorganisms. To investigate this question, we analyzed the immune responses of various inbred strains of mice to recombinant BCG expressing beta-galactosidase. These experiments demonstrated that BALB/c mice developed strong antibody responses against BCG expressing beta-galactosidase under the control of two different promoters. In contrast, C57BL/6, C3H, and CBA mice produced high anti-beta-galactosidase antibody titers only when immunized with recombinant BCG expressing beta-galactosidase under the control of the pblaF* promoter, which induced the production of high levels of ...

Infection and immunity, 1996

Among the various parameters which may contribute to Mycobacterium bovis BCG vaccination efficien... more Among the various parameters which may contribute to Mycobacterium bovis BCG vaccination efficiency, the choice of the vaccine strain may play an important role. In the present study, we therefore compared the immunogenicity of five different BCG strains that are commonly used for BCG vaccine production (Glaxo 1077, Japanese 172, Pasteur 1173P2, Prague, and Russian strains). The comparison of the growth capacity of these BCG strains in BALB/c and C3H mice demonstrated that a great difference exists between the capacity of various BCG strains to multiply and persist in target organs. A much lower recovery of BCG could be shown in mice immunized with Prague and Japanese BCG strains. T-cell responses of BCG-immunized mice were also examined by analyzing T-cell proliferative responses, cytokine production, delayed-type hypersensitivity responses, and cytotoxic activity. All these assays demonstrated that BCG immunization induced strong CD4+ T-cell responses, mostly of the Th1 type, as d...

We previously showed that treatment with Mycobacterium bovis BCG killed by extended freeze-drying... more We previously showed that treatment with Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) modulates inflammation through regulatory T cells (Tregs) in an acute asthma model. In this study, we investigated the kinetics of Treg induction as well as their long-term homing in spleen and lungs correlating with reduced airway hyperresponsiveness (AHR) in a murine model of acute allergic asthma. We then evaluated the therapeutic implication of EFD BCG in a chronic asthma model. Methods: Tregs expressing Foxp3 were analyzed in various organs shortly and long-term after EFD BCG, live-and Heat Killed-(HK-) BCG treatments in an acute model of asthma. We further studied EFD BCG treatment on airway inflammation using a chronic model of asthma in mice. Results: Foxp3 expression peaked in the inguinal draining lymph-nodes (iDLNs) 2 -4 days after EFD BCG treatment whereas it was long-term observed in spleen (days 7 to 90). This increase in Foxp3 expression was also found in lungs upon intranasal ovalbumin (OVA) challenge in OVA-sensitized mice. The loss of protection 4 months after EFD BCG treatment was correlated with the end of this phenomenon. Moreover, major lung inflammation hallmarks of severe asthma after multiple allergen challenges promoting chronic airway inflammation in OVA sensitized mice were reduced by EFD BCG treatment: AHR, eosinophils and neutrophils in bronchoalveolar lavage (BAL), mucus metaplasia, Th2 as well as Th17 cytokine levels in BAL and sera. EFD BCG treatment also enhances PPAR-γ expression and regulates NF-κBp65 translocation in lung extracts in this model of chronic asthma. Conclusions: EFD BCG treatment induced long-term protective effect associated to Foxp3 Tregs in the spleen and lungs in an acute model of asthma and inhibits AHR in a chronic model of asthma. EFD BCG could be a new and promising immuno-modulatory alternative treatment to corticoids in severe human asthma.

Revue des Maladies Respiratoires, 2007

Vaccines: A Biography, 2009

... Marina Gheorghiu, Micheline Lagranderie, and Anne-Marie Balazuc ... Another German physician,... more ... Marina Gheorghiu, Micheline Lagranderie, and Anne-Marie Balazuc ... Another German physician, Paul von Baumgarten, had indepen-dently and contemporaneously discovered the tubercle bacillus in infected tissue specimens (Brock 1999), but Koch received the public's ...

Science, 1998

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Vaccine, 2000

A variety of viral, bacterial and parasitic antigens have been expressed in BCG and the capacity ... more A variety of viral, bacterial and parasitic antigens have been expressed in BCG and the capacity of these recombinant bacteria to induce immune responses has been well documented. However, little is known about the parameters in¯uencing the induction of immune responses by recombinant BCG (rBCG), such as level of production and localization of the recombinant antigen. In the present study, we have constructed several rBCG strains expressing the malE gene from Escherichia coli which is either secreted or targeted to the cytoplasm or plasma membrane. Expression of malE was quanti®ed by ELISA and localization was analyzed by¯ow cytometry. Even when using the same promoter, levels of cytoplasmic or membrane MalE production were far less than those from secreting strains using either mycobacterial or E. coli secretion signals. Stronger and more rapid immune responses were induced by rBCG strains with the highest levels of secreted MalE compared to cytoplasmic or membrane constructs, including both good humoral and proliferative responses in BALB/c, C57BL6 and even C3H mice, previously shown to be poor MalE responders. These results suggest that the levels of foreign antigen production play an important role in the induction of immune responses by rBCG strains. 7

Vaccine, 1995

CTL responses are known to be important for the control of HIV and SIV infections. Such responses... more CTL responses are known to be important for the control of HIV and SIV infections. Such responses are targeted against various components of these viruses including regulatory proteins like Nef The SIV,,,,, nef gene was cloned in Mycobacterium bovis BCG under the control of P,,, a promoter from Mycobacterium paratuberculosis. Nef was expressed as a fusea'polypeptide with 0RF2, an open reading frame adjacent to P,,. Mice inoculated with rBCG( SI Vmar251 nef) exhibited proliferative and CD8+ cytotoxic

Vaccine, 1993

It has been shown recently that BCG can be used as a live recombinant vaccine to stimulate immune... more It has been shown recently that BCG can be used as a live recombinant vaccine to stimulate immune responses. Proliferative or cytotoxic T-cell responses against several viral proteins such as HIV Gag, Env or Nef were obtained after parenteral immunization with BCG expressing these proteins. Antibody responses were also obtained after immunization of mice with recombinant BCG strain which expressed lac Z under the control of a promoter sequence isolated from Mycobacterium paratuberculosis. We have used this recombinant vaccine in guinea-pigs to investigate the influence of various routes of immunization on the immunogenicity of a foreign antigen expressed by recombinant BCG. Guinea-pigs were immunized by oral, respiratory or intradermal routes and proliferative responses, delayed-type hypersensitivity and antibody responses specific for beta-galactosidase were followed for 16 weeks. Results demonstrated that humoral and cellular immune responses specific for beta-galactosidase can be produced in all groups of guinea-pigs. However, the respiratory and especially the oral route of administration induced higher local and systemic immune responses than the intradermal route of immunization. Moreover, the oral immunization of mice with this recombinant BCG induced IgA responses which could be detected in both sera and intestinal secretions. Therefore, this study demonstrates for the first time that oral immunization with recombinant BCG can induce strong cellular and humoral immune responses.

Vaccine, 2001

Two genes of Mycobacterium tuberculosis, apa (Rv1860) and pro (Rv1796), coding for two glycosylat... more Two genes of Mycobacterium tuberculosis, apa (Rv1860) and pro (Rv1796), coding for two glycosylated excreted proteins have been injected to mice and guinea pigs. They produce an extended immunological response of Th1 and Th2 types. Despite the fact that mycobacterial glycosylation is necessary for a high level of delayed-type hypersensitivity (DTH) reaction, plasmids bearing each of the two genes induced an elevated level of DTH sensitization. An inverse relation between the CpG-N hexamer cluster frequency and the protective effect of injected genes is described. A comparison of the strength of several eukaryotic promoters based on the diameter of the DTH reaction shows that CMVIE followed by the ubiquitin promoter are the most efficient among those tested. A significant protective effect (0.7 log unit CFU) in mice was found for the apa gene while the pro gene had no effect.

Scandinavian Journal of Immunology, 2002

Lagranderie M, Balazuc A-M, Abolhassani M, Chavarot P, Nahori M-A, Thouron F, Milon G, G Marchal.... more Lagranderie M, Balazuc A-M, Abolhassani M, Chavarot P, Nahori M-A, Thouron F, Milon G, G Marchal. Development of Mixed Th1/Th2 Type Immune Response and Protection Against Mycobacterium tuberculosis After Rectal or Subcutaneous Immunization of Newborn and Adult Mice with Mycobacterium bovis BCG. Scand J Immunol 2002;55:293±303

PLoS Pathogens, 2006

Influenza A virus (IAV) is the etiological agent of a highly contagious acute respiratory disease... more Influenza A virus (IAV) is the etiological agent of a highly contagious acute respiratory disease that causes epidemics and considerable mortality annually. Recently, we demonstrated, using an in vitro approach, that the pattern recognition Toll-like receptor (TLR)3 plays a key role in the immune response of lung epithelial cells to IAV. In view of these data and the fact that the functional role of TLR3 in vivo is still debated, we designed an investigation to better understand the role of TLR3 in the mechanisms of IAV pathogenesis and host immune response using an experimental murine model. The time-course of several dynamic parameters, including animal survival, respiratory suffering, viral clearance, leukocyte recruitment into the airspaces and secretion of critical inflammatory mediators, was compared in infected wild-type and TLR3 À/À mice. First, we found that the pulmonary expression of TLR3 is constitutive and markedly upregulated following influenza infection in control mice. Notably, when compared to wild-type mice, infected TLR3 À/À animals displayed significantly reduced inflammatory mediators, including RANTES (regulated upon activation, normal T cell expressed and secreted), interleukin-6, and interleukin-12p40/p70 as well as a lower number of CD8 þ T lymphocytes in the bronchoalveolar airspace. More important, despite a higher viral production in the lungs, mice deficient in TLR3 had an unexpected survival advantage. Hence, to our knowledge, our findings show for the first time that TLR3-IAV interaction critically contributes to the debilitating effects of a detrimental host inflammatory response. Citation: Le Goffic R, Balloy V, Lagranderie M, Alexopoulou L, Escriou N, et al. (2006) Detrimental contribution of the toll-like receptor (TLR)3 to influenza A virus-induced acute pneumonia. PLoS Pathog 2(6): e53.

Molecular Microbiology, 1992

A promoter sequence, P^N, was isolated from Mycobacterium paratuberculosis and characterized. Thi... more A promoter sequence, P^N, was isolated from Mycobacterium paratuberculosis and characterized. This promoter lies adjacent to, and outside, the 3' end of an ISdOO insertion element. ISdOO contains an open reading frame, 0RF2, on the complementary strand which codes for the putative transposase of this insertion sequence. A DNA fragment containing P^N and part of 0RF2 was fused to the IacZ gene and inserted into the replicative shuttle vector pRR3. Mycobacterium smegmatis and Mycobacterium bovis BCG (BCG) transformed with this piasmid exhibited |3-galactosidase activity. However, IacZ was only expressed in Escherichia coli under the control of PAN, when 0RF2 was deleted. Immunization of mice with the recombinant M. bovis BCG expressing IacZ resulted in the induction of a high humoral and cellular response directed against p-galactosidase. The PAfj~ORF2 expression system may prove to be particularly useful for cloning and expression of heterologous genes in the BCG vaccine strain.