Plasmacytoid dendritic cells (pDCs) play a major role in innate immunity producing large amounts of type I interferon following toll-like receptor (TLR) engagement. SOCS2 deficient mice have been shown to be hypersensitive to microbial infection but we found them to be much less susceptible to Sendai viral infection followed by heightened levels of serum type I IFN and reduced viral loads in lungs. To determine the role of SOCS2 in dendritic cell function, we analyzed DCs in peripheral lymphoid organs and tissues both under steady-state and inflammatory conditions. SOCS2-/- mice had markedly elevated pDCs during steady-state and these displayed higher expression of CCR7 and CXCR4. Following Sendai infection, we observed a significantly enhanced recruitment of pDCs into lungs with an elevated CXCR3, and CXCR4 receptor expression and enhanced pulmonary CXCL9, and CXCL12 gene expression on SOCS2 deficient lung tissues. SOCS2 deficiency did not affect pDC development in bone marrow and no overt change was observed in GM-CSF/STATS signalling on bone marrow pDCs. Enhanced ST AT5 early signalling response to GM-CSF stimulation in SOCS2-/- BM-derived and ex vivo pDCs suggests an important role for GM-CSF in promoting pDCs survival in SOCS2-/- animals. In addition, we observed no response of SOCS2-/- bone marrow pDCs and ex vivo pDCs to STAT3 activating cytokine signals (Flt3-L, lL-6). However, an evident level of activated STAT3 protein was observed in bone marrow pDCs and ex vivo pDCs under steady-state conditions. Collectively these results suggest that SOCS2 deficiency may play an important role in modulating viral immunity via promoting pDCs survival under steady-state conditions, and enhanced pDCs recruitment into inflamed organs following Sendai virus infection.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:580086 |
| Date | January 2012 |
| Creators | Singh, Sandhya |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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