The effect of human cytomegalovirus on innate immune responses : Immune activation and evasion

摘要: Human cytomegalovirus (HCMV) is a wide-spread virus infecting about 60-90 % of the healthy human population. After primary infection, establishes life-long latency in its host. Although HCMV seldom give any symptoms immunocompetent individuals, it may cause severe disease persons with deficient immune system, such as AIDS patients, transplant recipients and fetuses. The infection controlled mainly by virus-specific T cells NK cells, but to co-exist host, has developed several mechanisms influence host response. Reactivation mediated inflammation activated secretion strong pro-inflammatory cytokines, been linked inflammatory diseases bowel (IBD), systemic lupus erythematosus (SLE) cardiovascular disease. In addition, lately detected different tumors suggested play role cancers prostate cancer, colon cancer glioblastome multiforme (GBM). believed act an oncomodulatoty virus, contributing tumor cell growth survival. this thesis I aim further understand behind modulation how these effects contribute development cancer. describe that; (I) able partially stimulate PDC maturation induce IFN-α secretion. PDCs B activation proliferation conversely depress proliferation. This enhance virally immunosuppression help escape recognition. (II) cells. infected reduce cytotoxicity, instead facilitate non-cytotoxic cytokine producing are vital anti-viral response, viral evasion well induced reactivation replication. (III) Virally soluble molecules from vitro downregulate killing target Interestingly, positive glioblastoma demonstrated same inhibition cytotoxicity. observation describes mechanism which hampers function, led reduced anti-tumor responses. (IV) Peripheral neutrophil correlates progression patients GBM levels pro-and anti-inflammatry cytokines altered compared individuals. known activate neutrophils important inflammation, thereby dysfunction often seen patients. conclusion, ability alter system for reactivation. Here novel that LIST OF PUBLICATIONS based on following papers, will be referred their roman numerals: I. Varani S, Cederarv M, Feld Tammik C, Frascaroli G, Landini MP, SoderbergNaucler C. differentially controls responses through plasmacytoid dendritic J Immunol. 2007;179(11):7767-76. II. Odeberg J*, Soderberg-Naucler C*. deviates response into unable perform Immunobiology. 2009;214(5):331-41. III. Fritz N, Wolmer-Solberg Uhlen P, C* Specific suppression cytotoxicity Cytomegalovirus. Manuscript. IV. Rahbar Stragliotto, Peredo, I, Orrego A, Skarman Xu, X, Dzabic Taher Immunological patterns patients; PMNL activity associated progression. *Shared senior authorship