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.

Are circadian rhythms in disarray in patients with chronic critical illness?

Aim: The aim of our study is to assess circadian rhythms in patients with chronic critical illness due to severe brain injury in intensive care unit by establishing the relation between melatonin and cortisol secretion, considering astronomical time and the sleep-wake cycle in chronic critical illness.

Materials And Methods: The study included 54 adult patients with chronic critical illness who resided in the intensive care unit for at least 30 days. The level of consciousness was determined using the CRS-R scale.

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.

Prolonged B-Lymphocyte-Mediated Immune and Inflammatory Responses to Tuberculosis Infection in the Lungs of TB-Resistant Mice.

During tuberculosis (TB) infection, B-lymphocytes migrate to the lungs and form B-cell follicles (BCFs) in the vicinity of TB granulomata. B-cell-lacking mice display enhanced susceptibility to TB infection, and early B-cell depletion in infected non-human primates alters T-lymphocyte cytokine responses and increases bacterial burdens in the lungs. However, the role of B cells during late TB stages remained unaddressed.