In:
The Journal of Immunology, The American Association of Immunologists, Vol. 188, No. 1_Supplement ( 2012-05-01), p. 68.6-68.6
Abstract:
Respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract infection in infants and children worldwide. Dendritic cells (DC) prime the adaptive immune response by recognizing and delivering viral antigens to local lymph nodes, presenting antigen to T cells, displaying co-stimulatory markers, and releasing cytokines. Recent studies have linked macroautophagy to intracellular pathogen recognition and the activation of DCs leading to enhanced antigen-presenting cell (APC) function. SIRT1, a NAD+ dependent deacetylase, acts on many cellular substrates, including autophagy proteins (Atg), as shown with Sirt1-/- mice that accumulate damaged organelles similar to Atg5-/- mice. Our study investigates the role of SIRT1 in DC maturation, subsequent T cell activation, and RSV-induced pulmonary pathology. RSV infected bone marrow-derived DCs (BMDC) pre-treated with EX-527, a SIRT1 inhibitor, downregulate expression of key cytokines, MHCII, and CD86. EX527 treatment of RSV- infected wild-type mice resulted in increases in lung mucus production, viral load, and TH2 cytokine production. Likewise, EX527 significantly antagonizes TLR7-induced cytokine release in RSV-infected BMDCs, suggesting a link with the TLR/PAMP recognition response. These results suggest that SIRT1 may be a critical determinant in the innate immune response and resultant pulmonary pathology during RSV infection.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.188.Supp.68.6
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2012
detail.hit.zdb_id:
1475085-5
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