Papers by Anne-Marie Balazuc
Journal of Allergy and Clinical Immunology, 2008
Veterinary Immunology and Immunopathology, 2009
Tuberculosis occurred in humans probably as early as 8,000 bc in its sporadic form. Indeed, it is... more Tuberculosis occurred in humans probably as early as 8,000 bc in its sporadic form. Indeed, it is mentioned in India’s Vedas, the most sacred texts of Hinduism, and later by Hippocrates, Celse D’Aretée de Cappadoce (170 bc), and Avicene (Calmette 1923; Calmette et al. 1928). Recently, genetic studies of the tubercle bacillus have found its progenitor to come into existence possibly as early as 35,000 bc (Gutierrez et al. 2005). Tuberculosis became an epidemic problem once humans settled and crowded into permanent, food-producing social networks. Thus, Egyptian mummies from the Rhamses period (3,000 bc) showed spinal deformities consistent with tuberculosis – Pott’s disease. Hippocrates used the term “phthisis,” the Greek term for “consumption,” to describe the wasting away experienced by individuals with tuberculosis. Swollen cervical lymph nodes were known as “scrofula” or the “King’s Evil” in England (Artenstein et al. 1995). The belief that they could be healed by the King’s touch, although coincidentally true in some cases, likely had more to do with host immune responses than regal intervention.
Immunology, 2003
We showed in a previous study that the intranasal (i.n) delivery of bacille Calmette-Guérin (BCG)... more We showed in a previous study that the intranasal (i.n) delivery of bacille Calmette-Guérin (BCG) to BP2 mice (H-2 q ) inhibits eosinophilia and bronchial hyperreactivity in a mouse model of asthma. The present work has been performed to characterize the leucocyte lineages recruited to the lungs of mice after i.n. delivery of BCG and potentially involved in the polarization of T lymphocytes. The different antigen-presenting cells (APC) recruited to bronchoalveolar lavage (BAL) and to lung tissue of mice shortly after the delivery of BCG were analysed in parallel as well as their capacity to drive the immune response towards a T helper type 1 cytokine production. Alveolar macrophages (AM) from the BAL were CD11c þ , F4/80 þ and CD11b À , and in the lung tissue two major populations of potential APC were detected: one CD11c À , F4/80 þ , CD11b þ and I-A qÀ was identified as interstitial macrophages (IM) and a second expressing CD11c þ and I-A qþ antigens, negative for CD11b and F4/80 markers as leucocytic dendritic cells (DC). Freshly isolated DC upregulated CD11b and CD40 antigens after overnight culture, but remained negative for CD8a antigen, suggesting a myeloid origin. Lung DC which produced high amount of interleukin (IL)-12 were potent inducers of naive CD4 þ T lymphocyte priming, as assessed by interferon-g (IFN-g) production by these naive CD4 þ T cells. Lung explants recovered long term after BCG delivery produced sustained levels of IFN-g. Our results suggest that AM and particularly DC by secreting IL-12 shortly after BCG delivery induce the long-term persistence of IFN-g-secreting T cells percolating in BCG-loaded lung tissue.
Aids Research and Human Retroviruses, 1998
Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing different human immunodeficien... more Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing different human immunodeficiency virus (HIV) or simian immunodeficiency (SIV) antigens could be good candidates for the development of vaccines against AIDS. To develop effective HIV/SIV vaccines, humoral and cellular immune responses directed against multiple antigens may be essential for the control of the infection. In this study we immunized BALB/c mice via different mucosal routes (oral, aerogenic, nasal, and rectal) with a mixture of three rBCG strains expressing, respectively, the entire SIVmac251 Nef protein, and large fragments of the Env and Gag proteins. All routes of immunization studied induced immunoglobulin A (IgA) antibodies against mycobacterial PPD, SIV Env, and SIV Gag antigens in feces and bronchial lavages as well as specific immunoglobulin G (IgG) in serum. Strong, specific cytotoxic responses of splenocytes against Nef, Env, and Gag was observed whatever the mucosal route of immunization. Therefore, mucosal vaccination with a cocktail of rBCG strains induces local, specific IgA, systemic IgG, and systemic CTLs against the three SIV antigens expressed. Rectal and oral routes seemed the most appropriate route of vaccination to be used to protect against SIV infection.
Microbes and Infection, 2010
Once in the mouse skin, Leishmania (L) amazonensis amastigotes are hosted by professional mononuc... more Once in the mouse skin, Leishmania (L) amazonensis amastigotes are hosted by professional mononuclear phagocytes such as dendritic cells (DCs). When monitored after parasite inoculation, the frequency of amastigote-hosting DCs is very low (<1%) in both the skin and skindraining lymph nodes. Therefore, we designed and validated an efficient procedure to purify live amastigotes-hosting DCs with the objective to facilitate quantitative and qualitative analysis of such rare cells. To this end, a L. amazonensis transgenic parasite expressing DsRed2 fluorescent protein was generated and added to mouse bone marrow-derived DC cultures. Then, a high speed sorting procedure, performed in BSL-2 containment, was setup to pick out only DCs hosting live amastigotes. This study reveals, for the first time, a unique transcript pattern from sorted live amastigotes-hosting DCs that would have been undetectable in unsorted samples. It was indeed possible to highlight a significant and coordinated up-regulation of L-arginine transporter and arginase2 transcripts in Leishmania-hosting DCs compared to un-parasitized DCs. These results indicate that arginine catabolism for polyamine generation is dominating over L-arginine catabolism for NO generation. In conclusion, this approach provides a powerful method for further characterisation, of amastigote-hosting DCs in the skin and the skin-draining lymph nodes.
Infection and Immunity, 2003
Early after the intranasal instillation of Bordetella bronchiseptica into mice, not only are matu... more Early after the intranasal instillation of Bordetella bronchiseptica into mice, not only are mature dendritic leukocytes recovered from lung parenchyma and bronchoalveolar lavage fluid but their numbers are also increased in the mediastinal lymph nodes and the nasal mucosa-associated lymphoid tissue. Later during the infectious process, the bacteria persist mainly in the nasal cavity.
Microbes and Infection, 2006
BCG rectal administration to newborn and adult mice induced protective immune responses against t... more BCG rectal administration to newborn and adult mice induced protective immune responses against tuberculosis. BCG reaches the sub-epithelial site and the draining mesenteric lymph nodes (MLNs), and dendritic cells (DC) could be recruited to these sites. Using polarized Caco-2 epithelial cells, we showed that BCG translocates epithelial cells to basolateral compartment. Delayed in newborn BALB/c mice, an important recruitment of CD11c+ DCs, was documented in the rectal lamina propria and the MLNs during the first two weeks after rectal BCG delivery. In MLNs, two major DC subtypes were observed: conventional DCs (cDCs) (B220-) and plasmacytoid DCs (pDCs) (B220+). CIRE, mouse DC-specific intracellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is predominantly expressed on pDCs and at a higher level on pDCs from the adult compared to newborn MLNs. cDCs with a higher capacity to induce the proliferation of naïve CD4+ T cells than pDCs, triggered CD4+ T cells to produce interferon-gamma whereas pDCs triggered them to release interleukin-10. Both DC subtypes equilibrates T cells as a source of microbicidal/microbiostatic signals and those acting as source of counter-inflammatory signals, preventing tissue damage and/or accelerating tissue repair. Thus, rectal delivery of BCG could be a safe and efficient route of vaccination against tuberculosis.
Antimicrobial Agents and Chemotherapy, 2003
Tuberculosis occurred in humans probably as early as 8,000 bc in its sporadic form. Indeed, it is... more Tuberculosis occurred in humans probably as early as 8,000 bc in its sporadic form. Indeed, it is mentioned in India’s Vedas, the most sacred texts of Hinduism, and later by Hippocrates, Celse D’Aretée de Cappadoce (170 bc), and Avicene (Calmette 1923; Calmette et al. 1928). Recently, genetic studies of the tubercle bacillus have found its progenitor to come into existence possibly as early as 35,000 bc (Gutierrez et al. 2005). Tuberculosis became an epidemic problem once humans settled and crowded into permanent, food-producing social networks. Thus, Egyptian mummies from the Rhamses period (3,000 bc) showed spinal deformities consistent with tuberculosis – Pott’s disease. Hippocrates used the term “phthisis,” the Greek term for “consumption,” to describe the wasting away experienced by individuals with tuberculosis. Swollen cervical lymph nodes were known as “scrofula” or the “King’s Evil” in England (Artenstein et al. 1995). The belief that they could be healed by the King’s touch, although coincidentally true in some cases, likely had more to do with host immune responses than regal intervention.
Immunology, 2003
We showed in a previous study that the intranasal (i.n) delivery of bacille Calmette-Guérin (BCG)... more We showed in a previous study that the intranasal (i.n) delivery of bacille Calmette-Guérin (BCG) to BP2 mice (H-2 q ) inhibits eosinophilia and bronchial hyperreactivity in a mouse model of asthma. The present work has been performed to characterize the leucocyte lineages recruited to the lungs of mice after i.n. delivery of BCG and potentially involved in the polarization of T lymphocytes. The different antigen-presenting cells (APC) recruited to bronchoalveolar lavage (BAL) and to lung tissue of mice shortly after the delivery of BCG were analysed in parallel as well as their capacity to drive the immune response towards a T helper type 1 cytokine production. Alveolar macrophages (AM) from the BAL were CD11c þ , F4/80 þ and CD11b À , and in the lung tissue two major populations of potential APC were detected: one CD11c À , F4/80 þ , CD11b þ and I-A qÀ was identified as interstitial macrophages (IM) and a second expressing CD11c þ and I-A qþ antigens, negative for CD11b and F4/80 markers as leucocytic dendritic cells (DC). Freshly isolated DC upregulated CD11b and CD40 antigens after overnight culture, but remained negative for CD8a antigen, suggesting a myeloid origin. Lung DC which produced high amount of interleukin (IL)-12 were potent inducers of naive CD4 þ T lymphocyte priming, as assessed by interferon-g (IFN-g) production by these naive CD4 þ T cells. Lung explants recovered long term after BCG delivery produced sustained levels of IFN-g. Our results suggest that AM and particularly DC by secreting IL-12 shortly after BCG delivery induce the long-term persistence of IFN-g-secreting T cells percolating in BCG-loaded lung tissue.
Aids Research and Human Retroviruses, 1998
Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing different human immunodeficien... more Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing different human immunodeficiency virus (HIV) or simian immunodeficiency (SIV) antigens could be good candidates for the development of vaccines against AIDS. To develop effective HIV/SIV vaccines, humoral and cellular immune responses directed against multiple antigens may be essential for the control of the infection. In this study we immunized BALB/c mice via different mucosal routes (oral, aerogenic, nasal, and rectal) with a mixture of three rBCG strains expressing, respectively, the entire SIVmac251 Nef protein, and large fragments of the Env and Gag proteins. All routes of immunization studied induced immunoglobulin A (IgA) antibodies against mycobacterial PPD, SIV Env, and SIV Gag antigens in feces and bronchial lavages as well as specific immunoglobulin G (IgG) in serum. Strong, specific cytotoxic responses of splenocytes against Nef, Env, and Gag was observed whatever the mucosal route of immunization. Therefore, mucosal vaccination with a cocktail of rBCG strains induces local, specific IgA, systemic IgG, and systemic CTLs against the three SIV antigens expressed. Rectal and oral routes seemed the most appropriate route of vaccination to be used to protect against SIV infection.
Microbes and Infection, 2010
Once in the mouse skin, Leishmania (L) amazonensis amastigotes are hosted by professional mononuc... more Once in the mouse skin, Leishmania (L) amazonensis amastigotes are hosted by professional mononuclear phagocytes such as dendritic cells (DCs). When monitored after parasite inoculation, the frequency of amastigote-hosting DCs is very low (<1%) in both the skin and skindraining lymph nodes. Therefore, we designed and validated an efficient procedure to purify live amastigotes-hosting DCs with the objective to facilitate quantitative and qualitative analysis of such rare cells. To this end, a L. amazonensis transgenic parasite expressing DsRed2 fluorescent protein was generated and added to mouse bone marrow-derived DC cultures. Then, a high speed sorting procedure, performed in BSL-2 containment, was setup to pick out only DCs hosting live amastigotes. This study reveals, for the first time, a unique transcript pattern from sorted live amastigotes-hosting DCs that would have been undetectable in unsorted samples. It was indeed possible to highlight a significant and coordinated up-regulation of L-arginine transporter and arginase2 transcripts in Leishmania-hosting DCs compared to un-parasitized DCs. These results indicate that arginine catabolism for polyamine generation is dominating over L-arginine catabolism for NO generation. In conclusion, this approach provides a powerful method for further characterisation, of amastigote-hosting DCs in the skin and the skin-draining lymph nodes.
Infection and Immunity, 2003
Early after the intranasal instillation of Bordetella bronchiseptica into mice, not only are matu... more Early after the intranasal instillation of Bordetella bronchiseptica into mice, not only are mature dendritic leukocytes recovered from lung parenchyma and bronchoalveolar lavage fluid but their numbers are also increased in the mediastinal lymph nodes and the nasal mucosa-associated lymphoid tissue. Later during the infectious process, the bacteria persist mainly in the nasal cavity.
Microbes and Infection, 2006
BCG rectal administration to newborn and adult mice induced protective immune responses against t... more BCG rectal administration to newborn and adult mice induced protective immune responses against tuberculosis. BCG reaches the sub-epithelial site and the draining mesenteric lymph nodes (MLNs), and dendritic cells (DC) could be recruited to these sites. Using polarized Caco-2 epithelial cells, we showed that BCG translocates epithelial cells to basolateral compartment. Delayed in newborn BALB/c mice, an important recruitment of CD11c+ DCs, was documented in the rectal lamina propria and the MLNs during the first two weeks after rectal BCG delivery. In MLNs, two major DC subtypes were observed: conventional DCs (cDCs) (B220-) and plasmacytoid DCs (pDCs) (B220+). CIRE, mouse DC-specific intracellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is predominantly expressed on pDCs and at a higher level on pDCs from the adult compared to newborn MLNs. cDCs with a higher capacity to induce the proliferation of naïve CD4+ T cells than pDCs, triggered CD4+ T cells to produce interferon-gamma whereas pDCs triggered them to release interleukin-10. Both DC subtypes equilibrates T cells as a source of microbicidal/microbiostatic signals and those acting as source of counter-inflammatory signals, preventing tissue damage and/or accelerating tissue repair. Thus, rectal delivery of BCG could be a safe and efficient route of vaccination against tuberculosis.
Antimicrobial Agents and Chemotherapy, 2003
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Papers by Anne-Marie Balazuc