Abstract
Rhinovirus infections are linked to the development and exacerbation of allergic diseases including allergic asthma. IgE, another contributor to atopic disease pathogenesis, has been shown to regulate dendritic cell antiviral functions and influence T cell priming by monocytes. We previously demonstrated that IgE-mediated stimulation of monocytes alters multiple cellular functions including cytokine secretion, phagocytosis, and influenza-induced Th1 priming. In this study, we investigate the effects of IgE-mediated allergic stimulation on monocyte-driven, RV-induced T cell priming utilizing primary human monocyte-T cell co-cultures. We demonstrate that IgE crosslinking of RV-exposed monocytes enhances monocyte-driven Th2 priming while inhibiting Th1 differentiation. This increase in RV-induced Th2 differentiation was regulated by IgE-mediated induction of IL-10 and inhibition of type I interferon. These findings suggest an additional mechanism by which two clinically significant risk factors for allergic disease exacerbations – IgE-mediated stimulation and rhinovirus infection, may synergistically promote Th2 differentiation and allergic inflammation.
- Abbreviations
- APC
- antigen presenting cell
- αIgE
- Rabbit anti-human IgE antibody
- FcεRI
- high-affinity IgE receptor
- IFN
- interferon
- IgG
- Rabbit whole IgG antibody
- IL
- interleukin
- PBMCs
- peripheral blood mononuclear cells
- pDC
- plasmacytoid dendritic cells
- rh
- recombinant human
- RV
- Rhinovirus
- Th
- CD4 helper T cell
- TLR
- toll-like receptor
- TNF
- tumor-necrosis factor
Footnotes
Funding Sources: NIH NIAID, R01-AI098077 (MAG), NIH NHLBI, T32-HL098040 (RKR), Pediatric Infectious Disease Society/Astra-Zeneca Fellow Award in Respiratory Virus Research (RKR), NIH NRSA, T32-AI005284 (DMP), NIH NIGMS, T32-GM008014 (DMP), Children’s Clinical Research Advisory Council (CCRAC) (MAG), William A. and Joyce M. Sellars Distinguished Chair in Allergy and Immunology (MAG)