Disadvantages of a SPARCling defense

Giving infecting bacteria a little freedom early on can be good for the host, according to a new study by Rotta et al. (page 657). Confining the bugs too quickly, they find, can tie up the immune cells that need to spread the word. Certain bacteria, such as Mycobacterium tuberculosis and Salmonella, are quickly surrounded by macrophages, dendritic cells, and other immune cells that seal off the invaders from surrounding tissue. The convergence of these cells creates immune cages— or granulomas—that contain several extracellular matrix proteins, including SPARC, which enhances collagen assembly. Rotta et al. now find that SPARC-induced collagen prevents Salmonella-laden dendritic cells from slipping out of granulomas to the nearest lymph node to alert T cells. In mice infected through the skin with an attenuated strain of Salmonella, bacteria were hemmed in by a SPARC-enhanced granuloma within a day. After 9 days, however, the bacteria breached the fortifications. In the resulting absence of bacterium-killing T cells, the bugs rapidly spread out into other organs, and the animals soon died. SPARC-deficient mice, on the other hand, never formed granulomas when they were infected with this crippled strain of Salmonella. Immune cells found the infection site but failed to coalesce because SPARC-formed collagen was absent, thereby allowing dendritic cells to reach lymph nodes. The mice thus fought off this initial infection and survived a later challenge with a virulent strain of Salmonella. The immune system's knee-jerk reaction in trapping bacteria right away might be initially protective for widely infecting bugs that invade via the airways or the blood rather than the skin. The current findings suggest that antibacterial vaccines injected through the skin might be more effective if they are coinjected with a SPARC-blocking molecule. An aged immune system has experienced CD8 + T cells to combat old enemies but is missing some of the fresh CD8 + T cells that are also needed, according to Yager et al. (page 711). The CD8 + T cell pool is finite and in flux throughout an individual's lifetime. Each infection strengthens the numbers of T cells specific to that infecting microbe. In time, the T cell pool thus becomes skewed: the large number antigen-specific clones decreases the number and diversity of remaining naive T cells. Yager et al. now show that this age-related shrinking of the naive T cell pool results in a loss of the ability to respond to epitopes for …