IFNγ and iNOS-Mediated Alterations in the Bone Marrow and Thymus and Its Impact on -Induced Thymic Atrophy.

Disseminated infection with the high virulence strain of 25291 leads to progressive thymic atrophy. We previously showed that -induced thymic atrophy results from increased glucocorticoid levels that synergize with nitric oxide (NO) produced by interferon gamma (IFNγ) activated macrophages. Where and how these mediators act is not understood.

Advances on the Role and Applications of Interleukin-1 in Tuberculosis.

Interleukin-1 (IL-1) is a key player in the immune response to pathogens due to its role in promoting inflammation and recruiting immune cells to the site of infection. In tuberculosis (TB), tight regulation of IL-1 responses is critical to ensure host resistance to infection while preventing immune pathology. In the mouse model of Mycobacterium tuberculosis infection, both IL-1 absence and overproduction result in exacerbated disease and mortality.

Deficiency in the glycosyltransferase Gcnt1 increases susceptibility to tuberculosis through a mechanism involving neutrophils.

Modulation of immunity and disease by glycans is increasingly recognized. However, how host glycosylation shapes and is shaped by tuberculosis remains poorly understood. We show that deficiency in the glucosaminyl (N-acetyl) transferase 1 (Gcnt1), a key enzyme for core-2 O-glycans biosynthesis, drives susceptibility to Mycobacterium tuberculosis infection.

Myeloid HIF-1α regulates pulmonary inflammation during experimental Mycobacterium tuberculosis infection.

The transcription factor hypoxia-inducible factor-1 alpha (HIF-1α) is a key regulator of the response and function of myeloid cells in hypoxic and inflammatory microenvironments. To define the role of HIF-1α in tuberculosis, the progression of aerosol Mycobacterium tuberculosis infection was analysed in mice deficient in HIF-1α in the myeloid lineage (mHIF-1α ). We show that myeloid HIF-1α is not required for the containment of the infection, as both wild-type (WT) and mHIF-1α mice mounted normal Th1 responses and maintained control of bacterial growth throughout infection.

IFN-γ-Dependent Reduction of Erythrocyte Life Span Leads to Anemia during Mycobacterial Infection.

Anemia is a frequent and challenging complication of mycobacterial infections. We used a model of disseminated infection in mice to investigate the mechanisms of mycobacteria-induced anemia. We found increased formation of RBC in the bone marrow and spleen of infected mice.