doi:10.1242/dmm.020867. long-term protection and prevent disease progression. infections causing the most deaths by infectious disease each year (5). To prevent the ongoing epidemic, it is essential to develop an effective vaccine that protects against lung disease. A major challenge to vaccine development, however, is accounting for Pirozadil bacterial immune evasion Rabbit Polyclonal to 5-HT-6 tactics. effectively modulates adaptive responses from within the intracellular niche in antigen-presenting cells (APCs) that prevent T cell responses from sterilizing the infection (3, 6). Current vaccination methods activate the very processes that targets. Thus, it is essential to understand how suppresses adaptive responses to develop new approaches that bypass spp. to inhibit T cell responses from within APCs and draw similarities with other persistent bacterial pathogens. We will then discuss new approaches that might allow a full understanding of the IMMUNE CELL INTERACTIONS is a facultative intracellular pathogen that resides inside APCs, including a variety of macrophage and dendritic cell (DC) subsets (7, 8). Upon inhalation of efficiently targets alveolar macrophages that line the alveoli (8). Ideally, the initial infection by would stimulate inflammation in alveolar macrophages to activate protective adaptive immune responses that quickly respond to the lung and eradicate the infection. However, alveolar macrophages do not robustly detect or respond to infection, which results in a blunted inflammatory response and delays adaptive immune activation over 2 weeks (8,C10). This delay is unlike other lung infections such as those caused by influenza virus or respiratory syncytial virus (11). These viral infections develop a robust pathogen-specific T cell response within 1 week, suggesting that actively uses the alveolar macrophages to avoid rapid adaptive immune activation and detection. Eventually, antigens are trafficked to the draining lymph nodes by dendritic cells, where they activate infection, they must receive two distinct signals in the lung draining lymph node (14). Signal one is dependent on the antigen specificity of the T cell receptor (TCR) which detects pathogen-derived peptides loaded into major histocompatibility complex class I or II (MHC-I or MHC-II, respectively) (14). These peptide-MHC complexes are then presented on the surface of APCs to naive T cells. The second signal, also known as costimulation, is delivered to the T cell through the ligation of inflammation-induced molecules such as CD80, CD86, or CD40 on the surface of the APC (15, 16). Binding of distinct costimulatory molecule by T cells can skew their function, enhancing or inhibiting control (6, 17). In addition to signals one and two, a third signal, driven by stimulatory cytokines, enhances the activation of T cells, in particular, CD8+ T cells (reviewed in reference 4). Following their Pirozadil activation in the lymph node, T cells then traffic to the lung environment in search of infected cells to eradicate (13). In the lungs, direct contact of both CD4+ T cells and CD8+ T cells with cells harboring can partially control disease, yet they are insufficient to sterilize the infection (4, 13, 18). The reasons T cells fail to fully control infection are complex. actively prevents effective detection by T cells and drives T cell exhaustion that limits the protective potential of T cells (3, 7). Pirozadil It is also possible that evolved to use T cell responses to help drive transmission. Unlike viruses like influenza virus, which actively evade immunity by mutating antigens to prevent detection, does Pirozadil not evolve rapidly, and T cell antigens are known to be hyperconserved, with few mutations across lineages (19, 20). This means that the antigens activating the T cell responses are very conserved across the human population. This has led some to hypothesize that actively stimulates robust T cell responses to drive tissue damage and subsequent transmission. Together, these data suggest that T cells are essential to protect against infection, yet their role in disease progression needs to be more carefully Pirozadil understood. While T cells are required for protection against tuberculosis (TB), how T cells contribute to protection continues to be unclear mechanistically. T cells can defend by managing antimicrobial level of resistance pathways which restrict bacterial development or by regulating disease tolerance straight, the capability to withstand contamination and the next injury (1, 21). Considering that T cells cannot offer sterilizing.