tetano
Editor, Senior Moderator
Microbiol Immunol. 2016 Oct 12. doi: 10.1111/1348-0421.12443. [Epub ahead of print]
[h=1]Highly pathogenic avian influenza H5N1 virus induced cytokine dysregulation with suppressed maturation of chicken monocyte derived dendritic cells.[/h] Kalaiyarasu S[SUP]1[/SUP], Kumar M[SUP]2[/SUP], Kumar DS[SUP]2[/SUP], Bhatia S[SUP]2[/SUP], Dash SK[SUP]3[/SUP], Bhat S[SUP]3[/SUP], Khetan RK[SUP]2[/SUP], Nagarajan S[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] One of the major causes of death in highly pathogenic avian influenza virus (HPAIV) infection in chicken is due to acute induction of pro-inflammatory cytokine (cytokine storm) which leads to severe pathology and acute mortality. Dendritic cells and macrophages of respiratory tract are the major antigen presenting cells (APCs) getting exposed to mucosal pathogens. We hypothesized that chicken dendritic cells might be a major target for H5N1 HPAIV for induction of cytokine dysregulation. Infection of chMoDCs with H5N1 HPAIV produced high titers of progeny virus with more rounding and cytotoxicity than H9N2 LPAIV. Compared to LPS control group, low level of expression of maturation markers (CD40, CD80 and CD83) were observed in both H5N1 and H9N2 groups. Interferons α, β and γ were significantly upregulated in H5N1 group. The pro-inflammatory cytokines were highly upregulated in early (IL-1β, TNF-α factor and IL-18), mid (IL-1) and late (IL-6) phases of H5N1 virus infection. The level of IL-8 (CXCLi2) mRNA expression was significantly higher in H5N1 group from 6h of infection. TLR3, 7, 15 and 21 were upregulated at 24h of infection of H5N1 virus compared to H9N2 virus with maximum expression of TLR 3 mRNA. Similarly, H5N1 virus induced higher apoptotic cell death and cytotoxicity which were measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and lactate dehydrogenase (LDH) assays, respectively. This study revealed that both H5N1 and H9N2 viruses induced impairment of chMoDCs maturation to evade the host immune system with enhanced cytokine dysregulation in H5N1 HPAIV infected cells.
? 2016 The Societies and John Wiley & Sons Australia, Ltd.
[h=4]KEYWORDS:[/h] Avian Influenza; Chemokine; Cytokine; Monocyte derived dendritic cells
PMID: 27730669 DOI: 10.1111/1348-0421.12443
[PubMed - as supplied by publisher]
[h=1]Highly pathogenic avian influenza H5N1 virus induced cytokine dysregulation with suppressed maturation of chicken monocyte derived dendritic cells.[/h] Kalaiyarasu S[SUP]1[/SUP], Kumar M[SUP]2[/SUP], Kumar DS[SUP]2[/SUP], Bhatia S[SUP]2[/SUP], Dash SK[SUP]3[/SUP], Bhat S[SUP]3[/SUP], Khetan RK[SUP]2[/SUP], Nagarajan S[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] One of the major causes of death in highly pathogenic avian influenza virus (HPAIV) infection in chicken is due to acute induction of pro-inflammatory cytokine (cytokine storm) which leads to severe pathology and acute mortality. Dendritic cells and macrophages of respiratory tract are the major antigen presenting cells (APCs) getting exposed to mucosal pathogens. We hypothesized that chicken dendritic cells might be a major target for H5N1 HPAIV for induction of cytokine dysregulation. Infection of chMoDCs with H5N1 HPAIV produced high titers of progeny virus with more rounding and cytotoxicity than H9N2 LPAIV. Compared to LPS control group, low level of expression of maturation markers (CD40, CD80 and CD83) were observed in both H5N1 and H9N2 groups. Interferons α, β and γ were significantly upregulated in H5N1 group. The pro-inflammatory cytokines were highly upregulated in early (IL-1β, TNF-α factor and IL-18), mid (IL-1) and late (IL-6) phases of H5N1 virus infection. The level of IL-8 (CXCLi2) mRNA expression was significantly higher in H5N1 group from 6h of infection. TLR3, 7, 15 and 21 were upregulated at 24h of infection of H5N1 virus compared to H9N2 virus with maximum expression of TLR 3 mRNA. Similarly, H5N1 virus induced higher apoptotic cell death and cytotoxicity which were measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and lactate dehydrogenase (LDH) assays, respectively. This study revealed that both H5N1 and H9N2 viruses induced impairment of chMoDCs maturation to evade the host immune system with enhanced cytokine dysregulation in H5N1 HPAIV infected cells.
? 2016 The Societies and John Wiley & Sons Australia, Ltd.
[h=4]KEYWORDS:[/h] Avian Influenza; Chemokine; Cytokine; Monocyte derived dendritic cells
PMID: 27730669 DOI: 10.1111/1348-0421.12443
[PubMed - as supplied by publisher]