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.

Efficacy of macozinone in mice with genetically diverse susceptibility to Mycobacterium tuberculosis infection.

Host heterogeneity in pulmonary tuberculosis leads to varied responses to infection and drug treatment. The present portfolio of anti-TB drugs needs to be boosted with new drugs and drug regimens. Macozinone, a clinical-stage molecule targeting the essential enzyme, DprE1, represents an attractive option.

The H2-A Class II molecule α/β-chain mismatch severely affects cell surface expression, selection of conventional CD4 T cells and protection against TB infection.

Introduction: To dissect the role of the part of the complex comprised of the MHC-II genes in the control of tuberculosis (TB) infection, we previously established a panel of recombinant congenic mouse strains bearing different segments of the haplotype on the B6 ( ) genetic background. Fine genetic mapping, gene sequencing and assessment of TB phenotypes resulted in identification of the gene as a major factor of TB control.

Methods: We further narrowed the MHC-II interval by spotting a new recombination event, sequencing newly established DNA configuration and establishing a mouse strain B6.

Attenuated Strain of Mycobacterium tuberculosis BN: Characteristics.

We evaluated the vaccine properties of a novel attenuated strain of M. tuberculosis BN (Mtb BN) and its impact on the gut microbiota in inbred female mice in comparison with a virulent strain Mtb H37Rv and a vaccine strain BCG. The Mtb BN strain demonstrated the highest anti-tuberculosis vaccine effect in I/St mice highly susceptible to tuberculosis infection and the same effect as BCG in mice of the recombinant strain B6.

Thiazide and thiazide-like diuretics: how to make the right choice?

Most patients with arterial hypertension (AH) require a combination treatment to achieve the goal blood pressure. According to Russian and international clinical guidelines on the treatment of AH patients, various antihypertensive drugs may be combined; however, not all combinations have similar profiles of safety and clinical efficacy. In this respect, special attention is given to combinations of renin-angiotensin-aldosterone system inhibitors and thiazide (hydrochlorothiazide) or thiazide-like (chlortalidone, indapamide) diuretics.