Deficient in PdtaS Cytosolic Histidine Kinase Displays Attenuated Growth and Affords Protective Efficacy against Aerosol Infection in Mice.

New control measures are urgently required to control tuberculosis (TB), as the current vaccine, Bacille Calmette-Guérin (BCG), has had a limited impact on disease spread. The identification of virulence mechanisms of is an important strategy in vaccine design, as it permits the development of strains attenuated for growth that may have vaccine potential. In this report, we determined the role of the PdtaS response regulator in virulence and defined the vaccine potential of a -deficient strain.

Langerin CD8α Dendritic Cells Drive Early CD8 T Cell Activation and IL-12 Production During Systemic Bacterial Infection.

Bloodstream infections induce considerable morbidity, high mortality, and represent a significant burden of cost in health care; however, our understanding of the immune response to bacteremia is incomplete. Langerin CD8α dendritic cells (DCs), residing in the marginal zone of the murine spleen, have the capacity to cross-prime CD8 T cells and produce IL-12, both of which are important components of antimicrobial immunity. Accordingly, we hypothesized that this DC subset may be a key promoter of adaptive immune responses to blood-borne bacterial infections.

The Ag85B protein of the BCG vaccine facilitates macrophage uptake but is dispensable for protection against aerosol Mycobacterium tuberculosis infection.

Defining the function and protective capacity of mycobacterial antigens is crucial for progression of tuberculosis (TB) vaccine candidates to clinical trials. The Ag85B protein is expressed by all pathogenic mycobacteria and is a component of multiple TB vaccines under evaluation in humans. In this report we examined the role of the BCG Ag85B protein in host cell interaction and vaccine-induced protection against virulent Mycobacterium tuberculosis infection.

Sustained in vivo depletion of splenic langerin(+) CD8α(+) dendritic cells is well-tolerated by lang-DTREGFP mice.

Splenic langerin(+) CD8α(+) dendritic cells (DCs) have exhibited a critical role in cross-priming CD8(+) T cell responses. To further study the roles of this DC subset, a protocol for the continuous depletion of langerin(+) CD8α(+) DCs was established using the pre-existing lang-DTREGFP mouse model. Due to the fast turnover rate of splenic CD8α(+) DCs, maintaining the depletion of langerin(+) CD8α(+) DCs required multiple diphtheria toxin (DT) treatments.

Dendritic cell subsets in mycobacterial infection: control of bacterial growth and T cell responses.

Anti-mycobacterial immunity is guided by specialised antigen presenting cells known as dendritic cells, which are essential for both initiating and maintaining T cell immune responses during infection. The dendritic cell population can be divided into functionally distinct subsets that differ in their ability to present antigen and produce key TH1 cytokines, such as IL-12. This review discusses recent studies, in murine models, investigating which dendritic cell populations are important for mycobacterial control.