Polygenic TB control and the sequence of innate/adaptive immune responses to infection: MHC-II alleles determine the size of the S100A8/9-producing neutrophil population.

Among several quantitative trait loci involved in tuberculosis (TB) control in mice, one was mapped within the chromosome 17 segment occupied by the H2 complex and another within the chromosome 3 segment comprising the S100A8/9 genes, which encode neutrophil inflammatory factor S100A8/9. Previously, we developed a panel of H2-congenic mouse strains differing by small segments of the major histocompatibility complex Class II (MHC-II) region from TB-susceptible H2 mice transferred onto the genetic background of the TB-resistant C57BL/6 (H2) strain. Susceptible B6.

An In Vivo Model of Separate Phagocytosis by Neutrophils and Macrophages: Gene Expression Profiles in the Parasite and Disease Development in the Mouse Host.

The role of neutrophils in tuberculosis infection remains less well studied compared to that of the CD4 T-lymphocytes and macrophages. Thus, alterations in transcription profile following phagocytosis by neutrophils and how these shifts differ from those caused by macrophage phagocytosis remain unknown. We developed a mouse model that allows obtaining large amounts of either neutrophils or macrophages infected in vivo with for mycobacteria isolation in quantities sufficient for the whole genome RNA sequencing and aerosol challenge of mice.

Prolonged infection triggered by dormant Mycobacterium tuberculosis: Immune and inflammatory responses in lungs of genetically susceptible and resistant mice.

We developed an approach for substantial attenuation of Mycobacterium tuberculosis by prolonged culturing under gradually acidifying conditions. Bacteria subjected to acidification lost the capacity to form colonies on solid media, but readily resuscitated their growth in the murine host, providing a useful model to study in vivo development of infection mimicking latent and reactivation tuberculosis (TB) in humans. Here we characterize biomarkers of lung pathology and immune responses triggered by such attenuated bacteria in genetically TB-susceptible and resistant mice.

A new model for chronic and reactivation tuberculosis: Infection with genetically attenuated Mycobacterium tuberculosis in mice with polar susceptibility.

TB infection in mice develops relatively rapidly which interferes with experimental dissection of immune responses and lung pathology features that differ between genetically susceptible and resistant hosts. Earlier we have shown that the M. tuberculosis strain lacking four of five Rpf genes (ΔACDE) is seriously attenuated for growth in vivo.

Overexpression of Adenylyl Cyclase Encoded by the Rv2212 Gene Confers Improved Fitness, Accelerated Recovery from Dormancy and Enhanced Virulence in Mice.

Earlier we demonstrated that the adenylyl cyclase (AC) encoded by the gene plays a key role in the resuscitation and growth of dormant and that overexpression of this gene leads to an increase in intracellular cAMP concentration and prevents the transition of from active growth to dormancy in an extended stationary phase accompanied by medium acidification. We surmised that the homologous gene of (), the main cAMP producer, plays similar physiological roles by supporting, under these conditions, the active state and reactivation of dormant bacteria. To test this hypothesis, we established strain overexpressing and compared its and growth characteristics with a control strain.