Also during chronic LCMV infection, IL-6 has recently been identified to be a key molecule acting on CD4+ T cells during late stages of

chronic VX770 infection [[88]]. Signals via the IL-6 receptor on CD4+ T cells drove their differentiation into Tfh cells in a BCL-6 dependent manner. Furthermore, increased numbers of Tfh cells were essential for germinal center formation, LCMV-specific antibody production and subsequent viral control. Another CD4+ T-cell subset, which gains more and more interest in the context of chronic antigen exposure is the Treg cell subset. In particular, the ability of viruses to induce Treg cells, which subsequently suppress effector CD8+ T-cell responses appears to be a crucial viral escape mechanism [[89, 90]]. It was shown experimentally, that transient depletion of Treg cells during chronic Friend

retrovirus infection is sufficient to reinvigorate virus-specific CD8+ T-cell responses, thereby decreasing virus load [[91]]. For more detailed information on Ceritinib mw the role of Treg cells in the context of host-microorganism interactions we would like to refer to an excellent review by Belkaid and Tarbell [[92]]. Due to the complexity and the differences among the diverse immunization/infection models with respect to the antigen amounts, the nature of the inflammatory response present during the priming process of CD8+ T cells, the ability of the pathogen or adjuvant to induce DC maturation and the precursor frequencies of the responding CD8+ T cells, there are still unresolved controversies concerning the overall requirement of T-cell help, including the time points and mechanisms that are implicated selleck products in the delivery of help for CD8+ T-cell responses. Hence, further studies are needed focusing in particular on the molecular differences between helped and “helpless” memory CD8+ T cells, as well as on the mechanisms employed by CD4+ T cells to impact on the generation of potent effector CD8+ T

cells and proliferation-competent memory CD8+ T cells, in the context of defined experimental models. In the future, such comparative studies are likely to reveal “public” and “private” patterns of the T-cell help (in-)dependence of CD8+ T-cell responses, which will be instrumental in tailoring T-cell based vaccines. “
“Traversal of pathogen across the blood–brain barrier (BBB) is an essential step for central nervous system (CNS) invasion. Pathogen traversal can occur paracellularly, transcellularly, and/or in infected phagocytes (Trojan horse mechanism). To trigger the translocation processes, mainly through paracellular and transcellular ways, interactions between protein molecules of pathogen and BBB are inevitable. Simply, it takes two to tango: both host receptors and pathogen ligands. Underlying molecular basis of BBB translocation of various pathogens has been revealed in the last decade, and a plethora of experimental data on protein–protein interactions has been created.