Tularemia Vaccination and BALT Figure 7. Morphometric analysis of follicles and pulmonary dendritic cells at 30 days post-challenge. Data are expressed as average size of (A) and area occupied by (B) lymphoid and B cell follicles (mm2). (C) Dendritic cells (DCs) are shown from one representative mouse immunized with LPS+PorB and challenged with LVS (the two panels show different fields of the same lung where cells were detected). DCs were detected within follicles by CD11b (green), CD11c (red) or both (color overlap) and characterized by cytoplasmic prolongations. DCs are indicated by the yellow arrows. The white arrow on the left panel indicates a macrophage, characterized by a rounded shape. ** (P,0.01). Sections were viewed with a 206 objective. doi:10.1371/journal.pone.0011156.g007 repetitive intranasal stimulation (vaccination) followed by chal- lenge with LVS contributed to an increased organization of the follicles facilitating local activation of cells from the innate (macrophages, dendritic cells) and adaptive immune system (B cells and T cells). Our results support a potential beneficial role of BALT in the host infected with F. tularensis. In humans the role of BALT is unknown, and it is still unclear whether newly induced organized lymphoid follicles are either beneficial or detrimental for the host [44]. Most adult healthy human lungs present little evidence of these structures [24], but similar areas have been previously found in patients with pulmonary conditions, infectious diseases like tuberculosis and complications of autoimmune disease, where iBALT plays a role in lung immunopathology [34,37,45]. Since the structures we find in the current study appear in mice surviving infection when bacteria are cleared from the target organs, the direct translational significance of our findings into human immunity is presently difficult to define. Interesting future studies that could support our findings in the mouse model may include analysis of BALT in lung tissue from patients who have recovered versus those who have died from PLoS ONE | www.plosone.org 9 June 2010 | Volume 5 | Issue 6 | e11156