tetano
Editor, Senior Moderator
J Virol. 2015 Mar 25. pii: JVI.00296-15. [Epub ahead of print]
[h=1]CpG Oligodeoxynucleotides Facilitate Delivery of Whole Inactivated H9N2 Influenza Virus via Transepithelial Dendrites of Dendritic Cells in Nasal Mucosa.[/h] Qin T[SUP]1[/SUP], Yin Y[SUP]1[/SUP], Yu Q[SUP]1[/SUP], Huang L[SUP]1[/SUP], Wang X[SUP]1[/SUP], Lin J[SUP]1[/SUP], Yang Q[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The spread of the low pathogenic avian H9N2 influenza virus has seriously increased the risk of a new influenza pandemic. Although whole inactivated virus (WIV) vaccine via intranasal pathway is the effective method of blocking virus transmission, mucosal barrier seems to a major development-hampering factor. CpG oligodeoxynucleotides (CpG ODN), a known adjuvant, can target downstream dendritic cells (DCs) and effectively enhance the mucosal and systemic immune responses. However, the ability of CpG ODN to assist H9N2 WIV in transepithelial transport remains unknown. Here, in vitro and in vivo, we showed that CpG ODN provided assistance for H9N2 WIV in recruiting DCs to the nasal epithelial cells (ECs), and forming transepithelial dendrites (TEDs) to capture luminal viruses. CD103[SUP]+[/SUP] DCs participated in this process. Chemokine CCL20 from nasal ECs played a key role in driving DCs recruitment and TEDs formation. Viruses-loaded DCs quickly migrated into the draining cervical lymph nodes (CLNs) for antigen presentation. In addition, the competence of CpG ODN was independent of direct epithelial transport via transcellular or paracellular pathway. Taken together, our data demonstrated that CpG ODN enhanced the transport of H9N2 WIV via TEDs of nasal DCs, which might be a novel mechanism for the optimal adaptive immune responses.
[h=4]IMPORTANCE:[/h] This paper demonstrates both in vivo and in vitro coculture model that CpG ODN, a known adjuvant that generally target downstream immune responses, also are crucial for transport of H9N2 WIV across nasal epithelial cells (ECs) via transepithelial dendrites (TEDs) uptake. Our results prove for the first time to our knowledge that the immune-potentiating mechanism of CpG ODN is based on to strengthen transepithelial uptake of H9N2 WIV in nasal mucosa. These findings provide a fresh perspective for further improvement of intranasal influenza vaccines, which are urgently needed in the face of the potential threat of H9N2 influenza.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25810544 [PubMed - as supplied by publisher]
[h=1]CpG Oligodeoxynucleotides Facilitate Delivery of Whole Inactivated H9N2 Influenza Virus via Transepithelial Dendrites of Dendritic Cells in Nasal Mucosa.[/h] Qin T[SUP]1[/SUP], Yin Y[SUP]1[/SUP], Yu Q[SUP]1[/SUP], Huang L[SUP]1[/SUP], Wang X[SUP]1[/SUP], Lin J[SUP]1[/SUP], Yang Q[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The spread of the low pathogenic avian H9N2 influenza virus has seriously increased the risk of a new influenza pandemic. Although whole inactivated virus (WIV) vaccine via intranasal pathway is the effective method of blocking virus transmission, mucosal barrier seems to a major development-hampering factor. CpG oligodeoxynucleotides (CpG ODN), a known adjuvant, can target downstream dendritic cells (DCs) and effectively enhance the mucosal and systemic immune responses. However, the ability of CpG ODN to assist H9N2 WIV in transepithelial transport remains unknown. Here, in vitro and in vivo, we showed that CpG ODN provided assistance for H9N2 WIV in recruiting DCs to the nasal epithelial cells (ECs), and forming transepithelial dendrites (TEDs) to capture luminal viruses. CD103[SUP]+[/SUP] DCs participated in this process. Chemokine CCL20 from nasal ECs played a key role in driving DCs recruitment and TEDs formation. Viruses-loaded DCs quickly migrated into the draining cervical lymph nodes (CLNs) for antigen presentation. In addition, the competence of CpG ODN was independent of direct epithelial transport via transcellular or paracellular pathway. Taken together, our data demonstrated that CpG ODN enhanced the transport of H9N2 WIV via TEDs of nasal DCs, which might be a novel mechanism for the optimal adaptive immune responses.
[h=4]IMPORTANCE:[/h] This paper demonstrates both in vivo and in vitro coculture model that CpG ODN, a known adjuvant that generally target downstream immune responses, also are crucial for transport of H9N2 WIV across nasal epithelial cells (ECs) via transepithelial dendrites (TEDs) uptake. Our results prove for the first time to our knowledge that the immune-potentiating mechanism of CpG ODN is based on to strengthen transepithelial uptake of H9N2 WIV in nasal mucosa. These findings provide a fresh perspective for further improvement of intranasal influenza vaccines, which are urgently needed in the face of the potential threat of H9N2 influenza.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25810544 [PubMed - as supplied by publisher]