Abnormal Activation of Myeloid Dendritic Cells in JORRP Patients and Associated with Disease Activity

Representing the first line of host defense against virus infections and an essential link between innate and adaptive immune response, the role of dendritic cells (DCs) in peripheral blood of juvenile-onset recurrent respiratory papillomatosis (JORRP) patients and association with disease activity were still not established.

In our present study, 28 JORRP patients and 28 age and sex matched healthy controls were enrolled. The percentage, phenotype and cytokine secretion of DC and was measured by flow cytometry. Plasma cytokine were detected by the enzyme-linked immunosorbent assay (ELISA).

We found that the percentage of myeloid DC (mDC) was significantly lower in JORRP patients compared to healthy controls and was negatively correlated with interval times, but not surgical times or disease onset. Moreover, the activation marker, CD40 and CD86 was significantly up-regulated on the surfaces of mDC in JORRP patients compared with healthy controls. Neither the percentage nor activation of plasmacytoid DC (pDC) showed statistical difference between JORRP patients and healthy controls. HLA-DR expression on both mDC and pDC was down-regulated in JORRP group and negatively correlated with surgical times. Antigen presenting ability of DC was greatly impaired in JORRP patients of higher number of operations and shorter interval time. Plasma IL-10 as well as IL-10 secreted by mDC was higher in JORRP patients compared with healthy control. Finally, we detected an up-regulated TLR2 and TLR4 expression on mDCs and TLR4 expression was positively correlated with HLA-DR expression on mDC of JORRP patients.

Our results demonstrate an abnormal TLR2 and TLR4 expression in mDCs may contribute to suppressive immune response to HPV6 or HPV11 infection and associated with disease activity in JORRP patients.