(0.03 MB DOC) Click here for additional data file.(28K, doc) Alternative Language Abstract S2 Translation of the abstract into Spanish by Sharon Isern. (0.04 MB DOC) Click Ponatinib 284028-89-3 here for additional data file.(35K, doc) Footnotes The authors acknowledge that Florida Gulf Coast University, Tulane University, and the University of Washington have submitted patent applications covering the peptides described in this manuscript. Funding for this project was provided by DTRA awards HDTRA1-08-1-0003 and HDTRA1-09-1-0004 and NIH Shannon award 1-56-AI064617-01A2 to SI and SFM, and NSF CAREER award IIS-0448502 to RS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Immune protection against pathogens must be balanced co-evolutionarily against lethal damage by immune responses.
The process of host tissue destruction by the own immune system is termed immunopathology. Immunopathological sequel occurs during important infections in humans and mice. For example, after infection with hepatitis B and C virus in men, the T cell response causes liver cell damage. Similarly, the T cell response against lymphocytic choriomeningitis virus (LCMV) leads to destruction of secondary lymphoid organs, hepatic damage and choriomeningitis [1], [2]. Secondary lymphoid organs are highly organized structures, where B and T cells are localized to specialized zones. In contrast to lymph nodes, the lymphoid compartment of the spleen contains an additional structure called marginal zone, which consists of marginal zone macrophages, marginal zone metallophilic macrophages and marginal zone B cells [3].
Non-hematopoietic stromal cells orchestrate the structure of secondary lymphoid organs by expression of chemokines such as CCL19, CCL21, and CXCL13. The integrity of lymphoid organ architecture provides the basis for an optimal adaptive immune response. Mice with disturbed lymphoid organ architecture such as alymphoplastic (aly/aly), LT��R?/?, LT��?/?, LT��?/? and TNF��?/? mice have defects in the adaptive immune response of varying degree [4]. In addition to LCMV, destruction of lymphoid architecture is caused by several pathogens such as HIV [5], Plasmodium falciparum (malaria) [6] and Lassa virus [7] in men and Leishmania donovani [8], Borrelia crocidurae (relapsing fever) [9] and murine cytomegalovirus [10] in mice.
The destruction Entinostat of secondary lymphoid organs is therefore an effective strategy employed by pathogens to suppress the host’s immune system. The mechanisms of lymphoid organ architecture destruction are poorly defined in most of these infections, yet cytotoxic effects of the host’s immune system may play a central role. Immunopathology after LCMV infection has generally been attributed to cytotoxic CD8+ T cells, because CD8+ T cell depletion prevented the destruction of lymphoid organ architecture and hepatic damage [1], [11], [12].